@article{berman_birkenheuer_sorah_papich_2025, title={Analysis of US Marketed Artemisinin Supplements for Use in Dogs}, url={https://doi.org/10.1111/jvp.13480}, DOI={10.1111/jvp.13480}, abstractNote={ABSTRACT Oral artemisinin has antiparasitic activity and may help improve treatment success rates in dogs infected with Babesia gibsoni . However, these artemisinin products are unapproved and unregulated botanical supplements. They have not been evaluated for safety and efficacy or for strength, purity, or quality compared with a reference standard. Before considering these products for a clinical study, we evaluated the strength of four suppliers of artemisinin capsules using an high‐performance liquid chromatography method validated in our laboratory. We found that the four artemisinin‐labeled products that were tested had high within product and between product variability in capsule strength compared with the stated capsule strength on the product label. No products met the acceptance criteria of the United States Pharmacopeia and International Council for Harmonisation (ICH) as well as the criteria adapted by the authors. One product had no detectable artemisinin, and the other three products were much higher than the stated label strength. The results of this study reinforce the importance of testing unapproved and unregulated supplements before recommending a supplement for clinical use in dogs.}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Berman, Alyssa R. and Birkenheuer, Adam J. and Sorah, Emily L. and Papich, Mark G.}, year={2025}, month={Jan} }
 @article{gookin_papich_meier_enders_stauffer_wassack_davidson_2024, title={Auranofin is lethal against feline<i> Tritrichomonas</i><i> foetus</i> in vitro but ineffective in cats with naturally occurring infection}, volume={331}, ISSN={["1873-2550"]}, DOI={10.1016/j.vetpar.2024.110295}, journal={VETERINARY PARASITOLOGY}, author={Gookin, Jody L. and Papich, Mark G. and Meier, Elisa K. and Enders, Jeffrey and Stauffer, Stephen H. and Wassack, Erica E. and Davidson, Gigi S.}, year={2024}, month={Oct} }
 @article{trumbull_papich_peters_whitmer_rivard_field_2024, title={Comparative pharmacokinetics of a single oral dose of meloxicam in the California sea lion (<i>Zalophus californianus</i>) and Pacific harbor seal (<i>Phoca vitulina richardii</i>)}, volume={7}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/jvp.13469}, DOI={10.1111/jvp.13469}, abstractNote={Pharmacokinetics studies have investigated meloxicam, a non-steroidal anti-inflammatory drug, dosing strategies in a wide variety of non-domestic animals; however, there is no prior study examining well-founded dosing for pinnipeds. To develop dosing protocols, pharmacokinetic information is needed, with an examination of differences between pinniped species. Apparently, healthy California sea lions (Zalophus californianus: CSL; n = 13) and Pacific harbor seals (Phoca vitulina richardii: PHS; n = 17) that had completed rehabilitation were enrolled into a population-based pharmacokinetic study. Each animal was administered a single oral dose of meloxicam at 0.1 mg/kg, and two blood samples were collected from each animal at varying intervals during a 96-h study period. Plasma concentrations of meloxicam were determined by high-pressure liquid chromatography. Data were analyzed with nonlinear mixed effects modeling (Phoenix® NLME™, Certara, St. Louis, MO 63105, USA). The results indicated that in PHS, peak plasma concentration (C}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Trumbull, Emily J. and Papich, Mark G. and Peters, Mattison and Whitmer, Emily R. and Rivard, Michelle and Field, Cara L.}, year={2024}, month={Jul} }
 @article{lynch_ruterbories_zhu_fialkiewicz_papich_brooks_goggs_2024, title={Comparison of the pharmacokinetics and pharmacodynamics of apixaban and rivaroxaban in dogs}, volume={10}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.17216}, DOI={10.1111/jvim.17216}, abstractNote={Comparative pharmacokinetics and pharmacodynamics (PK/PD) of apixaban and rivaroxaban have not been studied in dogs and the propensity of these drugs to cause hypercoagulability after discontinuation is unknown.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Lynch, Alex M. and Ruterbories, Laura K. and Zhu, Yao and Fialkiewicz, Frank and Papich, Mark G. and Brooks, Marjory B. and Goggs, Robert}, year={2024}, month={Oct} }
 @article{lex_russell_mayer_padlo_boykin_papich_mitchell_2024, title={Determining the Pharmacokinetic Properties of Two Different Doses of Meloxicam in Barred Owls (<i>Strix varia</i>)}, volume={14}, ISSN={["2076-2615"]}, DOI={10.3390/ani14213086}, abstractNote={Anthropogenic activities have negatively affected many birds, including owls. The Wildlife Hospital of Louisiana (WHL) has seen a 3.2-fold increase in barred owl (Strix varia) cases over the past eight years (2023, 134; 2015, 42). Because most of these animals present with traumatic injuries, analgesics should be considered in their treatment plan. To date, no study has measured the pharmacokinetics of an analgesic in barred owls. The goals of this study were to determine the harmonic means, times to maximum concentration, and elimination half-lives for single 1 mg/kg and 2 mg/kg intramuscular doses of meloxicam. Twelve barred owls (1 mg/kg, n = 6; 2 mg/kg, n = 6) admitted to the WHL and determined to be clinically normal based on examination and blood work were recruited for this study. Meloxicam was administered intramuscularly, and blood samples were collected intermittently over 12 h to measure plasma concentrations using high-performance liquid chromatography. Both doses had rapid elimination half-lives (1 mg/kg, 0.99 ± 0.1 h; 2 mg/kg, 1.07 ± 0.43 h) and were below the limits of quantification (0.1 µg/mL) by 6–12 h. Based on these results, 1 and 2 mg/kg doses of meloxicam were found to produce plasma concentrations below therapeutic concentrations for less than four hours, making current twice-daily recommended dosing intervals unlikely to provide desired analgesia.}, number={21}, journal={ANIMALS}, author={Lex, Zoey N. and Russell, Laken and Mayer, Corinne and Padlo, Jordan and Boykin, Kimberly L. and Papich, Mark G. and Mitchell, Mark A.}, year={2024}, month={Nov} }
 @article{griffioen_fayette_proudfoot_howard_papich_2024, title={Penciclovir pharmacokinetics after oral and rectal administration of famciclovir in African elephants (Loxodonta africana) shows that effective concentrations can be achieved from rectal administration, despite lower absorption}, volume={85}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.24.02.0039}, abstractNote={Abstract OBJECTIVE To evaluate the pharmacokinetics of famciclovir and its metabolite penciclovir following a single dose administered orally and rectally in African elephants ( Loxodonta africana ). ANIMALS 15 African elephants (6 males and 9 females) of various ages. METHODS Famciclovir (15 mg/kg) was administered orally or per rectum once, with at least a three-week washout period between administrations. Blood was collected at 13 different timepoints per administration for 6 elephants, occurring between February and March 2020. An additional 9 elephants were sampled at variable timepoints per administration utilizing a sparse sampling design between July 2020 and January 2021. Plasma famciclovir and penciclovir levels were measured via HPLC and fluorescence detection. Pharmacokinetic analysis was completed in the summer of 2021 using noncompartmental analysis and nonlinear mixed-effects modeling. RESULTS Famciclovir was not detected in any sample, suggesting complete metabolism. Key pharmacokinetic parameters for penciclovir following oral administration were time to maximum concentration (t max ; 2.12 hours), area under the concentration-versus-time curve (AUC; 33.93 μg·h/mL), maximum observed concentration (C max ; 3.73 μg/mL), and absorption half-life (t 1/2 ; 0.65 hours). Following rectal administration, the values were: t max , 0.65 hours; AUC, 15.62 μg·h/mL; C max , 2.52 μg/mL; and absorption t 1/2 , 0.13 hours. CONCLUSIONS Famciclovir was rapidly metabolized to penciclovir. Oral administration resulted in slower absorption but higher maximum plasma concentration and higher AUC compared to rectal administration. CLINICAL RELEVANCE African elephants administered famciclovir via oral and rectal routes resulted in measurable serum penciclovir, and these findings may be utilized by clinicians treating viral infections in this species.}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Griffioen, John A. and Fayette, Melissa A. and Proudfoot, Jeffry S. and Howard, Lauren L. and Papich, Mark G.}, year={2024}, month={Jul} }
 @article{foster_halleran_jacob_hempstead_borst_watanabe_enomoto_papich_2025, title={Pharmacokinetics of pradofloxacin, florfenicol, and tulathromycin and response to treatment of steers experimentally infected with <i>Mannheimia hemolytica</i>}, volume={39}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.17270}, DOI={10.1111/jvim.17270}, abstractNote={Bovine respiratory disease (BRD) is an economically important disease in the beef industry, and a major driver of therapeutic antibiotic use. Pharmacokinetic data of these drugs is relatively limited in diseased animals.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Foster, Derek M. and Halleran, Jennifer L. and Jacob, Megan E. and Hempstead, Stephanie and Borst, Luke B. and Watanabe, Tatiane T. Negrao and Enomoto, Hiroko and Papich, Mark G.}, year={2025}, month={Jan} }
 @article{berman_birkenheuer_sorah_papich_2024, title={Response to Correspondence on 'Analysis of US Marketed Artemisinin Supplements for Use in Dogs'}, volume={10}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.13487}, abstractNote={Journal of Veterinary Pharmacology and TherapeuticsEarly View LETTER TO THE EDITOR Response to Correspondence on 'Analysis of US Marketed Artemisinin Supplements for Use in Dogs' Alyssa R. Berman, Corresponding Author Alyssa R. Berman [email protected] orcid.org/0009-0008-7837-5677 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA Correspondence: Alyssa R. Berman ([email protected])Search for more papers by this authorAdam J. Birkenheuer, Adam J. Birkenheuer Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USASearch for more papers by this authorEmily L. Sorah, Emily L. Sorah Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USASearch for more papers by this authorMark G. Papich, Mark G. Papich Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USASearch for more papers by this author Alyssa R. Berman, Corresponding Author Alyssa R. Berman [email protected] orcid.org/0009-0008-7837-5677 Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA Correspondence: Alyssa R. Berman ([email protected])Search for more papers by this authorAdam J. Birkenheuer, Adam J. Birkenheuer Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USASearch for more papers by this authorEmily L. Sorah, Emily L. Sorah Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USASearch for more papers by this authorMark G. Papich, Mark G. Papich Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USASearch for more papers by this author First published: 14 October 2024 https://doi.org/10.1111/jvp.13487Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Early ViewOnline Version of Record before inclusion in an issue RelatedInformation}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Berman, Alyssa R. and Birkenheuer, Adam J. and Sorah, Emily L. and Papich, Mark G.}, year={2024}, month={Oct} }
 @article{bello_lorch_papich_kim_toribio_yan_xie_hill_phelps_2024, title={The effects of food on the pharmacokinetics of mycophenolate mofetil in healthy horses}, volume={2}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.13430}, abstractNote={AbstractAdditional immunomodulatory treatment is needed for the management of immune‐mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses. The aim of this study was to evaluate the pharmacokinetics of a single dose of MMF in healthy horses in the fed vs. fasted state. Six healthy Standardbred mares were administered MMF 10 mg/kg by a nasogastric (NG) tube in a fed and fasted state. A six‐day washout period was performed between the two doses. No statistically significant differences in mycophenolic acid (MPA) concentrations were seen at any time point apart from 8 h, when plasma metabolite concentrations were significantly higher in the fasted state compared to the fed state (p = .038). Evidence of enterohepatic recirculation was seen only in the fasted state; this did not yield clinical differences in horses administered a single‐dose administration but may be significant in horses receiving long‐term MMF treatment.}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Bello, Kaitlyn and Lorch, Gwendolen and Papich, Mark G. and Kim, Kyeongmin and Toribio, Ramiro E. and Yan, Liwei and Xie, Zhiliang and Hill, Kasey and Phelps, Mitch A.}, year={2024}, month={Feb} }
 @article{papich_2023, title={Antimicrobial agents in small animal dermatology for treating staphylococcal infections}, volume={261}, ISSN={["1943-569X"]}, DOI={10.2460/javma.23.01.0023}, abstractNote={
Abstract
Antibiotic recommendations for treating skin infections have been published many times in the past 30 years. Prior to 2000, the recommendations focused on the use of β-lactam antibiotics, such as cephalosporins, amoxicillin-clavulanate, or β-lactamase stable penicillins. These agents are still recommended, and used, for wild-type methicillin-susceptible strains of Staphylococcus spp. However, since the mid-2000s there has been an increase in methicillin-resistant Staphylococcus spp (MRSP). The increase among S pseudintermedius in animals coincided with the increase in methicillin-resistant S aureus that was observed in people near the same time. This increase led veterinarians to reevaluate their approach to treating skin infections, particularly in dogs. Prior antibiotic exposure and hospitalization are identified as risk factors for MRSP. Topical treatments are more often used to treat these infections. Culture and susceptibility testing is performed more often, especially in refractory cases, to identify MRSP. If resistant strains are identified, veterinarians may have to rely on antibiotics that were previously used uncommonly for skin infections, such as chloramphenicol, aminoglycosides, tetracyclines, and human-label antibiotics such as rifampin and linezolid. These drugs carry risks and uncertainties that must be considered before they are routinely prescribed. This article will discuss these concerns and provide veterinarians guidance on the treatment of these skin infections.
}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Papich, Mark G.}, year={2023}, month={Jun}, pages={S130–S139} }
 @article{hartman_hernandez_hendrix_risselada_weng_papich_kim_2023, title={Effects of storage up to 1 year on the in vitro antimicrobial activity of preformulated antibiotic-impregnated calcium sulfate beads}, volume={8}, ISSN={["1532-950X"]}, DOI={10.1111/vsu.14014}, abstractNote={AbstractObjectiveTo compare antimicrobial activity as demonstrated by the zone of inhibition (ZOI) produced by antibiotic‐impregnated calcium sulfate (CaSO4) beads after storage for 0, 3, 6, 9, and 12 months.Study designControlled laboratory study.Sample populationThree‐millimeter diameter CaSO4beads impregnated with vancomycin (125 mg/mL), or amikacin (250 mg/mL), or without antibiotic (control).MethodsCalcium sulfate beads were created at the onset of the study. Individual beads were separated in sterile containers and stored in a closed cabinet at room temperature and humidity for 0, 3, 6, 9, or 12 months until testing. The ZOI against methicillin‐resistantStaphylococcus pseudintermedius,methicillin‐resistantStaphylococcus aureus,andPseudomonas aeruginosawas recorded with serial replating on a fresh lawn of bacteria every 24 h until beads failed to produce a ZOI. The ZOIs and their changes were compared with mixed‐effects linear models. Eluted concentrations of vancomycin measured with high‐performance liquid chromatography were reported.ResultsAt 24 h, ZOIs were comparable regardless of time since formulation, except vancomycin againstP. aeruginosa,which failed to generate a ZOI. The daily changes of ZOI and duration of activity of antibiotics did not vary between storage length (p > .05). There was no consistent change in eluted drug concentration between storage length of beads.ConclusionLight protected storage at room temperature for up to 12 months did not impair the in vitro activity of antibiotic‐impregnated CaSO4beads, as demonstrated through ZOIs.Clinical significanceWhen stored correctly, antibiotic‐impregnated CaSO4beads can be used at least up to 12 months after formulation.}, journal={VETERINARY SURGERY}, author={Hartman, Emily Allyson and Hernandez, Daniela Pena and Hendrix, Gena Kenitra and Risselada, Marije and Weng, Hsin-Yi and Papich, Mark G. and Kim, Sun Young}, year={2023}, month={Aug} }
 @article{kilburn_schmitt_kiso_papich_backues_2022, title={PHARMACOKINETICS OF RECTALLY AND ORALLY ADMINISTERED LEVOFLOXACIN IN ASIAN ELEPHANTS (ELEPHAS MAXIMUS)}, volume={53}, ISSN={["1937-2825"]}, DOI={10.1638/2022-0011}, abstractNote={Abstract: Appropriate and effective antibiotic use is a critical component of veterinary medicine, but there are variations across species regarding dosage and administration of these drugs. Oral or rectal routes of administration are typically used in elephants, but not all medications can achieve adequate concentrations rectally. The fluoroquinolone antimicrobials are used in elephants because of their favorable antimicrobial spectrum and pharmacokinetics compared with other oral agents. They are commonly used as part of multiple antibiotic regimens for the treatment of tuberculosis (Mycobacterium tuberculosis). The objective of this study was to determine the pharmacokinetic profile of levofloxacin after oral and rectal administration in Asian elephants (Elephas maximus). Dosages of 5 mg/kg orally and 15 mg/kg rectally were evaluated in 13 Asian elephants. Blood was collected at various time points from 0 to 72 h for pharmacokinetic analysis. Pharmacokinetic parameters were determined and reached concentrations above minimum inhibitory concentrations of various bacterial organisms via both routes. A pharmacokinetic-pharmacodynamic assessment was used to estimate appropriate minimal inhibitory concentrations for bacteria that could be potentially treated with this antimicrobial. Based on these findings, levofloxacin may be a consideration for administration orally (5 mg/kg) and rectally (15 mg/kg) in Asian elephants. Antimicrobial stewardship principles, culture and susceptibility of suspected pathogens, and blood level monitoring should be used to tailor administration of levofloxacin in this species.}, number={4}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Kilburn, Jennifer J. and Schmitt, Dennis and Kiso, Wendy and Papich, Mark G. and Backues, Kay A.}, year={2022}, month={Dec}, pages={670–678} }
 @article{mcmanamey_defrancesco_meurs_papich_2023, title={Pharmacokinetics of pimobendan after oral administration to dogs with myxomatous mitral valve disease}, volume={9}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16891}, DOI={10.1111/jvim.16891}, abstractNote={AbstractBackgroundPimobendan is an important therapy for dogs with myxomatous mitral valve disease (MMVD). The pharmacokinetics are reported in healthy dogs but not in dogs with heart disease.Hypothesis/ObjectivesTo determine if dog characteristics such as age, breed, body condition score, ACVIM stage of heart disease or biochemical laboratory value alter the pharmacokinetics of orally administered pimobendan and its metabolite in a cohort of dogs with naturally occurring MMVD.AnimalsFifty‐seven client‐owned dogs with MMVD ACVIM Stage B2, C, or D and administered pimobendan to steady state blood concentrations.MethodsProspective, observational study. Samples were collected using a sparse‐sampling protocol at specific intervals after administration of pimobendan. Plasma pimobendan and the active metabolite (O‐desmethyl‐pimobendan, ODMP) concentrations were determined via high‐pressure liquid chromatography and fluorescence detection. Data was analyzed via a population pharmacokinetic approach and nonlinear mixed effects modeling (NLME). Numerous covariates were examined in the NLME model.ResultsThe absorption and elimination half‐lives (t1/2) were approximately 1.4 and 1 hour for pimobendan and 1.4 and 1.3 hours for ODMP, respectively. Pharmacokinetic parameters were highly variable, especially the values for pimobendan absorption and elimination rate, and absorption rate of ODMP with coefficients of variation of 147.84%, 64.51% and 64.49%, respectively. No covariate evaluated was a significant source of variability.Conclusions and Clinical ImportanceThe pharmacokinetic parameters were highly variable among this group of dogs with MMVD. The variability was not associated with the dog's age, body weight or condition score, stage of heart disease, dose, serum creatinine, or alkaline phosphatase.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={McManamey, Anna K. and DeFrancesco, Teresa C. and Meurs, Kathryn M. and Papich, Mark G.}, year={2023}, month={Sep} }
 @article{foster_abouraya_papich_muma_2023, title={Population pharmacokinetic analysis of enrofloxacin and its active metabolite ciprofloxacin after intravenous injection to cats with reduced kidney function}, volume={9}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16866}, DOI={10.1111/jvim.16866}, abstractNote={AbstractBackgroundIt is unknown if enrofloxacin accumulates in plasma of cats with reduced kidney function.HypothesisTo determine if enrofloxacin and its active metabolite ciprofloxacin have reduced clearance in azotemic cats.AnimalsThirty‐four cats hospitalized for clinical illness with variable degree of kidney function.MethodsProspective study. After enrofloxacin (dose 5 mg/kg) administration to cats, sparse blood sampling was used to obtain 2 compartment population pharmacokinetic results using nonlinear mixed‐effects modeling. Plasma enrofloxacin and ciprofloxacin concentrations were measured and summed to obtain the total fluoroquinolone concentration. A model of ciprofloxacin metabolism from enrofloxacin was created and evaluated for covariate effects on clearance, volume of distribution, and the metabolic rate of ciprofloxacin generation from enrofloxacin.ResultsBody weight was the only covariate found to affect total fluoroquinolone volume of distribution (effect 1.63, SE 0.19, P < .01) and clearance (effect 1.63, SE 0.27, P < .01). Kidney function did not have a significant effect on total fluoroquinolone clearance (median 440.8 mL/kg/h (range 191.4‐538.0 mL/kg/h) in cats with normal kidney function, 365.8 mL/kg/h (range 89.49‐1092.0 mL/kg/h) in cats with moderate kidney dysfunction, and 308.5 mL/kg/h (range 140.20‐480.0 mL/kg/h) in cats with severe kidney dysfunction (P = .64). Blood urea nitrogen concentration influenced the metabolic generation of ciprofloxacin from enrofloxacin (effect 0.51, SE 0.08, P < .01), but other markers of kidney function did not.Conclusions and clinical importance.Adjustment of enrofloxacin dosage is not indicated for azotemic cats.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Foster, Jonathan D. and Abouraya, Mahmoud and Papich, Mark G. and Muma, Nancy A.}, year={2023}, month={Sep} }
 @article{cabot_papich_harrison_thomson_defrancesco_ozawa_2023, title={Population pharmacokinetics of single dose oral pimobendan in the ferret (Mustela putorius furo)}, volume={48}, ISSN={["1931-6283"]}, url={https://doi.org/10.1053/j.jepm.2023.09.002}, DOI={10.1053/j.jepm.2023.09.002}, abstractNote={: Therapeutic options and dosing recommendations for congestive heart failure in the domestic ferret are currently extrapolated from domestic dogs and cats. The goal of this study was to determine the pharmacokinetics of oral pimobendan in the domestic ferret. : Twelve domestic ferrets were administered a single dose (average 0.4 mg/kg) of pimobendan in a commercially available, chewable, meat-flavored tablet formulation. High-performance liquid chromatography and fluorescence detection were used to measure pimobendan and the metabolite O-desmethylpimobendan (ODMP) in plasma samples collected at 0, 0.25, 0.5, 1, 2, 4, 6, 9, and 12 hours after administration using a sparse sampling protocol. : peak plasma concentration, 14.29 ng/mL and 16.88 ng/mL; time to peak plasma concentration, 1.69 hr and 1.97 hr; area under the curve, 129.87 ng*hr/mL and 190.97 ng*hr/mL; and elimination half-life, 4.97 hr and 6.32 hr, respectively. No adverse events were noted. : A single dose of oral pimobendan in ferrets reached concentrations higher than that reported for dogs by the manufacturer and similar to peak plasma concentrations correlated with a therapeutic effect in healthy dogs in a separate study. Individual variability was high and plasma concentrations in at least half of the ferrets remained at or below the lower limit of quantification throughout the duration of the study. Additional studies are needed to characterize the pharmacodynamics, oral bioavailability, and duration of action to facilitate dosing recommendations for pimobendan in the domestic ferret.}, journal={JOURNAL OF EXOTIC PET MEDICINE}, author={Cabot, Megan L. and Papich, Mark G. and Harrison, Tara M. and Thomson, Andrea E. and Defrancesco, Teresa and Ozawa, Sarah M.}, year={2023}, month={Jan}, pages={1–5} }
 @article{papich_gunnett_v. lubbers_2023, title={Revision of fluoroquinolone breakpoints used for interpretation of antimicrobial susceptibility testing of canine bacterial isolates}, volume={84}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.23.07.0159}, abstractNote={Abstract
The fluoroquinolone antimicrobial agents, enrofloxacin and marbofloxacin, were US Food and Drug Administration (FDA) approved in the United States for use in dogs in 1988 and 1999, respectively. There have been many advances since then concerning the pharmacokinetic-pharmacodynamic (PK-PD) evaluation of fluoroquinolones, and there are data available on the susceptibility of targeted pathogens since the original approval. Using this information, the Clinical and Laboratory Standards Institute (CLSI) Veterinary Antimicrobial Susceptibility Testing Subcommittee (VAST) revised its antimicrobial susceptibility testing breakpoints. The previous breakpoints (used in older editions of CLSI standards) for enrofloxacin in dogs were susceptible (S), ≤ 0.5 µg/mL, intermediate (I) 1–2 µg/mL, and resistant (R) ≥ 4 µg/mL. The new breakpoints are S ≤ 0.06 µg/mL for a dose of 5 mg/kg, 0.12 µg/mL for a dose of 10 mg/kg, 0.25 µg/mL for a high dose of 20 mg/kg, and R ≥ 0.5 µg/mL. The breakpoints of 0.12 and 0.25 µg/mL represent a new susceptible-dose dependent (SDD) category. For marbofloxacin, previous breakpoints were S, ≤ 1 µg/mL, I 2 µg/mL, and R ≥ 4 µg/mL. The new breakpoints are S ≤ 0.12 µg/mL for a dose of 2.8 mg/kg, 0.25 µg/mL for a dose of 5.5 mg/kg (SDD), and R ≥ 0.5 µg/mL. The new breakpoints will be published in the next edition of CLSI-Vet01(S) and deviate considerably from the prior breakpoints. Laboratories are encouraged to revise their testing standards. These changes will likely reduce the unnecessary use of these fluoroquinolones in dogs.}, number={11}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Papich, Mark G. and Gunnett, Lacie A. and V. Lubbers, Brian}, year={2023}, month={Nov} }
 @article{mcentire_landolfi_adkesson_papich_sander_roy_talley_vincent_allender_2023, title={THE PHARMACOKINETICS AND PHARMACODYNAMICS OF ORAL PONAZURIL IN THE TREATMENT OF SYSTEMIC ISOSPOROSIS IN PASSERINE BIRDS}, volume={54}, ISSN={["1937-2825"]}, DOI={10.1638/2022-0091}, abstractNote={Abstract: Systemic isosporosis, previously atoxoplasmosis, is a significant cause of mortality in juvenile passerine birds. Recommended treatment regimens are empiric and vary in efficacy. The goal of this study was to determine the pharmacokinetics and pharmacodynamics of ponazuril for treatment of systemic isosporosis. Ponazuril, diluted with water to create an oral suspension (50 mg/ml), was administered (100 mg/kg) to 72 European starlings (Sturnus vulgaris) by a single dose via direct oral gavage (n = 24), a single dose injected into superworm larvae (Zophobas morio; n = 24), or a daily dose mixed with commercial dog food to top-dress feed for 5 d (n = 24). Peak plasma concentrations were 5.84, 2.46, and 9.13 µg/ml for the direct gavage, injected larvae, and top-dressed feed groups, respectively. With repeated dosing, mean plasma concentrations from the top-dressed feed group were maintained between 8.12 to 13.11 µg/ml. Results suggested ponazuril at a dosage of 100 mg/kg administered via direct gavage or top-dressed feed, but not via injected larvae, would exceed the concentrations needed to inhibit merogony of other apicomplexan parasites in cell culture (5 µg/ml). To assess the pharmacodynamics of this dose, seven passerine birds, red-vented bulbuls (Pycnonotus cafer; n = 2), blue-grey tanager (Thraupis episcopus; n = 1), and red-capped cardinals (Paroaria gularis; n = 4), were identified as shedders of systemic Isospora spp. via fecal qPCR. Birds were then treated with ponazuril (100 mg/kg) daily on top-dressed feed for 14 d. Fecal shedding was assessed via qPCR for 6 wk from the initiation of treatment. Treatment was associated with reduction in proportions of fecal shedding during the treatment period and the week following treatment, but shedding resumed in all birds by the end of sampling. Results support that treatment of breeding birds with 100 mg/kg ponazuril could reduce the shedding of active oocysts and decrease risk of clinical infection in susceptible juveniles.}, number={3}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={McEntire, Michael S. and Landolfi, Jennifer A. and Adkesson, Michael J. and Papich, Mark G. and Sander, Samantha J. and Roy, Leena and Talley, Alexandria and Vincent, Lauren and Allender, Matthew C.}, year={2023}, month={Sep}, pages={561–572} }
 @article{papich_madsen_messenger_enomoto_2022, title={Ceftazidime pharmacokinetics in dogs after intravenous injection and delivered with the RxActuator Mini-Infuser infusion pump}, volume={5}, ISSN={["1476-4431"]}, url={https://doi.org/10.1111/vec.13205}, DOI={10.1111/vec.13205}, abstractNote={AbstractObjectiveTo test the feasibility of an SC mini‐infusion pump to deliver ceftazidime in dogs and produce plasma concentrations sufficient to reach a therapeutic target for 48 hours.SettingUniversity research laboratory.AnimalsSix healthy Beagle dogs.InterventionsCeftazidime was administered by 2 routes to 6 healthy Beagle dogs. The first route was an IV bolus injection into a cephalic vein at a dose of 25 mg/kg. Blood samples were collected for 8 hours following injection. The second route was a SC infusion for 48 hours using the RxActuator Mini‐Infuser wearable SC constant rate infusion pump. Blood samples were collected for 58 hours following application of the pump. All plasma samples were analyzed by high‐pressure liquid chromatography and subject to pharmacokinetic analysis.Main ResultsAfter the IV bolus injection, there was rapid distribution and elimination. The elimination half‐life was 0.95 hours, and the clearance was rapid at 0.176 ml/h/kg. After the 48‐hour SC infusion, the half‐life was slightly shorter, and the clearance was higher. The percent bioavailability from the SC infusion was approximately 72%. The SC infusion maintained plasma concentration near our target of 8 μg/ml for most of the dose interval but slightly lower after 24 hours. The concentrations below the target were attributed to slight drug loss, less than 100% bioavailability, and faster clearance from SC administration.ConclusionsThis study demonstrated the successful application of the RxActuator Mini‐Infuser wearable SC constant rate infusion pump for delivering an antimicrobial needed for serious, and sometimes resistant, infections in dogs.}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={Papich, Mark G. and Madsen, Melanie and Messenger, Kristen and Enomoto, Hiroko}, year={2022}, month={May} }
 @article{tolbert_telles_simon_scallan_price_gould_papich_lidbury_steiner_kathrani_2022, title={Gastrointestinal transit time is faster in Beagle dogs compared to cats}, volume={260}, ISSN={["1943-569X"]}, DOI={10.2460/javma.22.07.0287}, abstractNote={Abstract

OBJECTIVE
To characterize gastrointestinal transit times (GITTs) and pH in dogs, and to compare to data recently described for cats.


ANIMALS
7 healthy, colony-housed Beagles.


PROCEDURES
The GITTs and pH were measured using a continuous pH monitoring system. For the first period (prefeeding), food was withheld for 20 hours followed by pH capsule administration. Five hours after capsule administration, dogs were offered 75% of their historical daily caloric intake for 1 hour. For the second period (postfeeding), food was withheld for 24 hours. Dogs were allowed 1 hour to eat, followed by capsule administration. Both periods were repeated 3 times. The GITTs and pH were compared to published feline data.


RESULTS
The mean ± SD transit times in dogs for the pre- and postfeeding periods, respectively, were esophageal, 3 ± 5 minutes and 13 ± 37 minutes; gastric, 31 ± 60 minutes and 829 ± 249 minutes; and intestinal, 795 ± 444 minutes and 830 ± 368 minutes. The mean ± SD gastrointestinal pH in dogs for the pre- and postfeeding periods, respectively, were esophageal, 6.6 ± 0.6 and 5.7 ± 1.0; gastric, 3.0 ± 1.4 and 1.8 ± 0.3; intestinal, 7.9 ± 0.3 and 7.7 ± 0.6; first-hour small intestinal, 7.6 ± 0.5 and 7.1 ± 0.4; and last-hour large intestinal, 7.9 ± 0.6 and 7.7 ± 1.0. The first-hour small intestinal pH and total transit times varied between dogs and cats depending on feed period (P = .002 and P = .04, respectively). Post hoc analysis revealed significantly shorter total transit times in dogs prefeeding (P = .005; mean ± SD for cats, 2,441 ± 1,359 minutes; for dogs, 828 ± 439 minutes) and postfeeding (P = .03; mean ± SD for cats, 3,009 ± 1,220 minutes; for dogs, 1,671 ± 513 minutes). Total transit time for dogs was also shorter pre- versus postfeeding (P = .003).


CLINICAL RELEVANCE
GITT is faster in Beagles compared to cats, but gastrointestinal pH are similar when fed the same diet.
}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Tolbert, M. Katherine and Telles, Naila J. and Simon, Bradley T. and Scallan, Elizabeth M. and Price, Joshua M. and Gould, Emily N. and Papich, Mark G. and Lidbury, Jonathan A. and Steiner, Jorg M. and Kathrani, Aarti}, year={2022}, month={Dec}, pages={S8–S14} }
 @article{martinez_papich_fahmy_2022, title={Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics}, volume={1}, ISSN={["1848-7718"]}, url={https://doi.org/10.5599/admet.1140}, DOI={10.5599/admet.1140}, abstractNote={Many gaps exist in our understanding of species differences in gastrointestinal (GI) fluid composition and the associated impact of food intake and dietary composition on in vivo drug solubilization. This information gap can lead to uncertainties with regard to how best to formulate pharmaceuticals for veterinary use or the in vitro test conditions that will be most predictive of species-specific in vivo oral product performance. To address these challenges, this overview explores species-specific factors that can influence oral drug solubility and the formulation approaches that can be employed to overcome solubility-associated bioavailability difficulties. These discussions are framed around some of the basic principles associated with drug solubilization, reported species differences in GI fluid composition, types of oral dosage forms typically given for the various animal species, and the effect of prandial state in dogs and cats. This basic information is integrated into a question-and-answer section that addresses some of the formulation issues that can arise in the development of veterinary medicinals.}, journal={ADMET AND DMPK}, author={Martinez, Marilyn N. and Papich, Mark G. and Fahmy, Raafat}, year={2022}, month={Jan} }
 @article{kane_matthew r. o'connor_papich_2022, title={PHARMACOKINETICS OF A SINGLE DOSE OF INTRAMUSCULAR AND ORAL MELOXICAM IN YELLOW STINGRAYS (UROBATIS JAMAICENSIS)}, volume={53}, ISSN={["1937-2825"]}, DOI={10.1638/2021-0123}, abstractNote={Abstract: Elasmobranchs are popular display animals in public aquaria and zoos, but medical management gaps remain in the understanding of the pharmacokinetics of analgesics and pain management in these species. Meloxicam is a nonsteroidal anti-inflammatory drug that has been evaluated intravenously and intramuscularly in teleosts, but has yet to be studied in any elasmobranch species. The pharmacokinetics of meloxicam were determined in 17 yellow stingrays (Urobatis jamaicensis). All stingrays were determined to be healthy from complete physical examinations and baseline bloodwork performed prior to study inclusion. A single dose of 1 mg/kg meloxicam intramuscularly was administered to all rays, followed by a 2 mg/kg oral dose after an 8 wk washout period. Blood samples were collected from the mesopterygial vein at baseline and nine time points up to 96 h after administration of meloxicam. Plasma concentrations were determined using reversed-phase high-performance liquid chromatography. Pharmacokinetic analysis was performed using a noncompartmental technique. The mean peak plasma concentrations for intramuscular and oral meloxicam were 1.29 and 0.42 µg/ml, respectively. The mean terminal half-lives of meloxicam after intramuscular and oral administration were 5.75 and 15.46 h, respectively. Based on these findings, the recommended meloxicam dosage and frequency for yellow stingrays is 2 mg/kg orally once daily. Due to rapid elimination with the intramuscular administration, maintaining clinically relevant plasma concentrations may be difficult using this route. Further studies are needed to determine multidose pharmacokinetics of meloxicam in yellow stingrays, as well as single-dose and multidose pharmacokinetics in other elasmobranch species.}, number={1}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Kane, Lauren P. and Matthew R. O'Connor and Papich, Mark G.}, year={2022}, month={Mar}, pages={153–158} }
 @article{pusterla_vaala_bain_chappell_craig_schneider_barnett_gaughan_papich_2023, title={Pharmacokinetics of a FDA-labeled dose of diclazuril administered orally once weekly to adult horses}, volume={120}, ISSN={["1542-7412"]}, DOI={10.1016/j.jevs.2022.104183}, abstractNote={Equine protozoal myeloencephalitis (EPM) has remained a devastating neurological disease of the Americas, especially in young performance horses. Prophylactic treatment strategies with diclazuril have shown to reduce seroprevalence and titer levels to Sarcocystis neurona in healthy horses continuously exposed to the apicomplexan parasite. The goal of this study was to determine if the FDA-labeled dose of 1 mg/kg of 1.56% diclazuril (Protazil TM ) given once weekly to healthy adult horses would achieve steady-state concentrations in plasma known to be inhibitory to S. neurona in cell culture. Five individual diclazuril doses were administered at weekly intervals to 8 adult horses. Blood was collected via venipuncture immediately before (trough concentration) and 10 hours after (peak concentration) each diclazuril administration. Following the fifth dose, additional blood samples were collected every 24 hours after the peak blood collection for 7 days. All plasma samples were analyzed by high-pressure liquid chromatography. The pharmacokinetic analysis was performed using a nonlinear mixed effects model. The mean population-derived peak concentration was 264 ng/mL and the mean terminal half-life was 3.6 days. Thus, the oral administration of an FDA-labeled dose of diclazuril to healthy horses once a week was able to produce steady-state plasma drug concentrations known to inhibit S. neurona in vitro.}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Pusterla, Nicola and Vaala, Wendy and Bain, Fairfield T. and Chappell, Duane E. and Craig, Bryant and Schneider, Chrissie and Barnett, D. Craig and Gaughan, Earl and Papich, Mark G.}, year={2023}, month={Jan} }
 @article{bloch_papich_sturmer_2022, title={Veterinary antimicrobial prescribing practices for treatment of presumptive sporadic urinary tract infections in dogs examined at primary care practices in the United States (2010-2019)}, volume={260}, ISSN={["1943-569X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85132219765&partnerID=MN8TOARS}, DOI={10.2460/javma.21.03.0123}, abstractNote={Abstract

OBJECTIVE
To describe patterns of antimicrobial prescriptions for sporadic urinary tract infections (UTIs) in dogs in the United States from 2010 through 2019, including times before and after publication of International Society for Companion Animal Infectious Disease (ISCAID) guidelines.


SAMPLE
461,244 qualifying visits for sporadic UTIs.


PROCEDURES
Veterinary electronic medical records of a private corporation consisting of > 1,000 clinics across the United States were examined to identify canine visits for potential sporadic UTI between January 1, 2010, and December 31, 2019. Proportions of antimicrobial prescriptions were graphed by month and year to identify changes in prescription patterns over time. Interrupted time series analysis was performed for the aminopenicillins.


RESULTS
A total of 461,244 qualifying visits were examined, with 389,949 (85%) of these resulting in at least 1 antimicrobial prescription. Over the 10-year period, the proportion of visits resulting in no antimicrobial prescription increased (14% in 2010 to 19.7% in 2019). Proportions of prescriptions for amoxicillin (38% to 48%) and amoxicillin–clavulanic acid (2.5% to 10%) also increased. Log-linear regression supported that changes in proportions of amoxicillin and amoxicillin–clavulanic acid prescriptions occurred following the 2011 ISCAID guidelines publication, with the proportion of amoxicillin prescriptions increasing by 13% per year (95% CI, 12% to 14%; P < 0.01) and the proportion of amoxicillin–clavulanic acid prescriptions increasing by 0.5% per year (95% CI, 0.2% to 0.8%; P < 0.01). Use of fluoroquinolones and third-generation cephalosporins remained constant.


CLINICAL RELEVANCE
Results suggest that efforts to guide antimicrobial use in veterinary clinical practice are having positive effects in this private veterinary company, though continued efforts are warranted.
}, number={S2}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Bloch, Rebecca A. and Papich, Mark G. and Sturmer, Til}, year={2022}, month={Jun}, pages={S21–S27} }
 @article{monaghan_labato_papich_2021, title={Ampicillin pharmacokinetics in azotemic and healthy dogs}, volume={35}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16026}, DOI={10.1111/jvim.16026}, abstractNote={AbstractBackgroundLittle is known about effects of factors such as kidney disease, affecting ampicillin pharmacokinetics in dogs.ObjectivesDetermine the pharmacokinetics of ampicillin after a single intravenous dose in healthy and azotemic dogs.AnimalsNine dogs presenting with acute kidney injury and 10 healthy dogs.MethodsThis was a prospective study. An ampicillin dose of 22.2 mg/kg (mean dose) was administered once intravenously. Blood samples were obtained at timed intervals (just before administration, 1, 2, 4, 12, and 24 hours), analyzed using high‐pressure liquid chromatography followed by pharmacokinetic analysis of the plasma drug concentrations.ResultsPeak ampicillin concentration (mcg/mL; 97.07 (36.1) vs 21.3 (50.26)), P<.001 (geometric mean (coefficient of variation, CV%)), half‐life (hours; 5.86 (56.55) vs 0.97 (115.3)), P<.001) and AUC (h × mcg/mL; 731.04 (83.75) vs 33.57 (53.68)), P<.001) were greater in azotemic dogs than in healthy dogs. Azotemic dogs also had significantly lower clearance (30.06 (84.19) vs 655.03 (53.67); mL/kg h, P < .001) and volume of distribution (253.95 (30.14) vs 916.93 (135.24); mL/kg, P <.001) compared to healthy dogs.Conclusion and Clinical ImportanceIncreased drug concentrations and slower clearance of ampicillin in azotemic dogs could have clinical importance in contributing to antibiotic associated morbidity requiring indicating the need to adjust ampicillin dosing in dogs with decreased kidney function.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Monaghan, Kelly N. and Labato, Mary Anna and Papich, Mark G.}, year={2021}, month={Mar}, pages={987–992} }
 @misc{valitutto_yu_raphael_calle_sykes_pare_moore_papich_2021, title={CEFOVECIN PROTEIN BINDING AS A PREDICTOR FOR EXTENDED DURATION OF ACTION: A REVIEW OF CURRENT LITERATURE AND IN VITRO ANALYSIS IN MULTIPLE ZOOLOGICAL SPECIES}, volume={52}, ISSN={["1937-2825"]}, DOI={10.1638/2021-0068}, abstractNote={Abstract: Cefovecin is a third-generation cephalosporin antibiotic with an efficacy of 2 wk following a single injection in domestic dogs and cats. A high degree of plasma protein binding to cefovecin has been proposed as one of the mechanisms responsible for the long elimination half-life, but protein binding has not been evaluated extensively in nondomestic species. In this study, a review of the current literature was conducted, and pharmacokinetic data were compiled for species in which cefovecin has been evaluated thus far. Additionally, in vitro cefovecin protein binding was evaluated in plasma from 22 nondomestic species representing a broad range of taxa. Animals of the order Carnivora demonstrated protein-binding levels of >98%, which is supportive of the long elimination half-life seen in related species. Protein binding was highly variable in Artiodactyl and Perissodactyl species, with dolphins (Tursiops truncatus) and barasingha (Rucervus duvaucelii) displaying high protein binding (99.12% to >99%), but not gazelles (Eudorcas thomsonii) or equids (91.76–92.70%). Cefovecin was not highly bound in any reptiles or birds, corresponding to short half-lives reported for these taxa. These results suggest that a high percentage of plasma protein binding in vitro may predict in which species cefovecin may exhibit a long half-life and duration of action in vivo. These findings may aid in selecting species for cefovecin pharmacokinetic research and for empirical treatment of infections caused by susceptible bacteria.}, number={4}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Valitutto, Marc T. and Yu, Jennifer H. and Raphael, Bonnie L. and Calle, Paul P. and Sykes, John M. and Pare, Jean and Moore, Robert P. and Papich, Mark G.}, year={2021}, month={Dec}, pages={1185–1194} }
 @article{yu_papich_torres_emerson_kinney_helmick_crosier_sanchez_murray_2021, title={Cefovecin pharmacokinetics after single-dose intramuscular administration in cheetahs (Acinonyx jubatus)}, volume={44}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12969}, abstractNote={AbstractCefovecin is a third‐generation cephalosporin with potential value for use in exotic felids due to its long duration of action. A sparse sampling protocol was implemented with 18 zoo‐housed cheetahs (Acinonyx jubatus) to evaluate the pharmacokinetics of cefovecin (Convenia®) after a single 8 mg/kg intramuscular injection. Blood was collected serially for 15 days following administration, and plasma cefovecin concentrations were determined using high‐pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters were estimated using population pharmacokinetic methods and non‐linear mixed effects modeling (NLME). Cefovecin was well tolerated by all cats, with no adverse effects observed. Peak plasma cefovecin concentration was 84.75 µg/ml, with a mean residence time of 207.9 h and an elimination half‐life of 144.1 h (6.00 days). Plasma concentrations of cefovecin were maintained >7 µg/ml in all individuals for the entire study duration (15 days). These concentrations are lower, and the half‐life slightly shorter, than the values reported for domestic cats. Cefovecin was highly protein‐bound (approximately 99.9%) in cheetah plasma, which is nearly identical to domestic cats. These results indicate that cefovecin is potentially useful as a long‐acting antibiotic in cheetahs.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Yu, Jennifer H. and Papich, Mark G. and Torres, Rodrigo Garces and Emerson, Jessica and Kinney, Matthew E. and Helmick, Kelly and Crosier, Adrienne and Sanchez, Carlos R. and Murray, Suzan}, year={2021}, month={Sep}, pages={829–835} }
 @article{beachler_papich_andrews_dollen_ellis_withowski_bailey_2021, title={Clinical Outcome of Transcervical Infusion of a Combination of Procaine Penicillin and Gentamicin in Late-term Pregnant Mares}, volume={106}, ISSN={["1542-7412"]}, DOI={10.1016/j.jevs.2021.103727}, abstractNote={Transcervical intrauterine infusion of antibiotics may more effectively treat pathogens associated with fetal and neonatal disease in pregnant mares than standard systemic routes. The objective of this study was to assess the safety of transcervical antibiotic infusion by characterizing the gestational outcome in nine healthy pregnant pony mares following a single transcervical infusion of 2.4 million IU of procaine penicillin and 200 mg of gentamicin in a 10 mL volume during late gestation. Assessment of fetal-placental health was performed through serial measurement of the combined thickness of the uterus and placenta (CTUP) and fetal heart rate and mares and foals were closely monitored in the periparturient period. Fetal heart rate and CTUP remained unchanged after infusion, with no evidence of fluid accumulation or significant increase at the time-points 24, 48, and 72 hours. All mares foaled without complication 12-58 days after antibiotic infusion at a mean gestational age of 322.7 ± 12.7 days. Two out of nine foals displayed signs of mild neonatal maladjustment syndrome that responded to minimal supportive care and all foals survived to weaning without further complications.}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Beachler, Theresa M. and Papich, Mark G. and Andrews, Natalie C. and Dollen, Karen A. Von and Ellis, Katelyn E. and Withowski, Katie and Bailey, Christopher Scott}, year={2021}, month={Nov} }
 @article{halleran_callahan_jacob_sylvester_prange_papich_foster_2021, title={Effects of danofloxacin dosing regimen on gastrointestinal pharmacokinetics and fecal microbiome in steers}, volume={11}, ISSN={["2045-2322"]}, DOI={10.1038/s41598-021-90647-z}, abstractNote={AbstractFluoroquinolones are a class of antimicrobial commonly used in human medicine, and deemed critical by the World Health Organization. Nonetheless, two formulations are approved for the treatment of respiratory disease in beef cattle. The objective of this study was to determine the gastrointestinal pharmacokinetics and impact on enteric bacteria of cattle when receiving one of the two dosing regimens (high: 40 mg/kg SC once or low: 20 mg/kg IM q48hr) of danofloxacin, a commonly utilized synthetic fluoroquinolone in veterinary medicine. Danofloxacin was administered to 12 steers (age 7 months) fitted with intestinal ultrafiltration devices at two different dosing regimens to assess the gastrointestinal pharmacokinetics, the shifts in the gastrointestinal microbiome and the development of resistant bacterial isolates. Our results demonstrated high intestinal penetration of danofloxacin for both dosing groups, as well as, significant differences in MIC values for E. coli and Enterococcus between dosing groups at selected time points over a 38 day period. Danofloxacin treatment consistently resulted in the Euryarchaeota phyla decreasing over time, specifically due to a decrease in Methanobrevibacter. Although microbiome differences were minor between dosing groups, the low dose group had a higher number of isolates with MIC values high enough to cause clinically relevant resistance. This information would help guide veterinarians as to appropriate dosing schemes to minimize the spread of antimicrobial resistance.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Halleran, J. L. and Callahan, B. J. and Jacob, M. E. and Sylvester, H. J. and Prange, T. and Papich, M. G. and Foster, D. M.}, year={2021}, month={May} }
 @article{madsen_enomoto_messenger_papich_2022, title={Effects of housing environment on oral absorption of acetaminophen in healthy Beagles}, volume={83}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.21.06.0075}, abstractNote={Abstract

OBJECTIVE
To evaluate the effects of housing environment on oral absorption of acetaminophen in dogs.


ANIMALS
6 healthy Beagles.


PROCEDURES
Acetaminophen (325 mg, PO; mean dose, 31.1 mg/kg) was administered in a crossover study design with dogs housed in their normal environment or in a cage in an unfamiliar environment. There was a 7-day washout period between phases. Blood samples were collected for 24 hours following acetaminophen administration, and plasma acetaminophen concentrations were determined with high-pressure liquid chromatography.


RESULTS
A 2-compartment model with lag time was the best fit for both phases of the study. None of the primary or secondary pharmacokinetic parameters were significantly different between the 2 housing environments.


CLINICAL RELEVANCE
Findings suggested that in dogs, housing environment (normal environment vs a cage in an unfamiliar environment) did not significantly affect oral absorption and, by extension, gastric emptying of acetaminophen.
}, number={1}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Madsen, Melanie and Enomoto, Hiroko and Messenger, Kristen and Papich, Mark G.}, year={2022}, month={Jan}, pages={80–85} }
 @article{telles_simon_scallan_gould_papich_he_lee_lidbury_steiner_kathrani_et al._2021, title={Evaluation of gastrointestinal transit times and pH in healthy cats using a continuous pH monitoring system}, volume={12}, ISSN={["1532-2750"]}, DOI={10.1177/1098612X211062096}, abstractNote={Objectives The aim of this study was to characterize gastrointestinal (GI) transit times and pH in healthy cats. Methods GI transit times and pH were measured in six healthy, colony-housed, purpose-bred spayed female cats using a continuous, non-invasive pH monitoring system in a sequential order design. For the first period (‘pre-feeding’), food was withheld for 20 h, followed by oral administration of a pH capsule. Five hours post-capsule administration, cats were meal-fed by offering them their daily allowance of food for 1 h. For the second period (‘post-feeding’), food was withheld for 24 h and cats were fed for 1 h, after which a pH capsule was orally administered. Studies in both periods were repeated three times. GI transit times and pH were compared between the two periods. Results The median transit times for the pre- and post-feeding periods, respectively, were: gastric – 94 mins (range 1–4101) and 1068 mins (range 484–5521); intestinal – 1350 mins (range 929–2961) and 1534 mins (range 442–2538); and GI – 1732 mins (range 1105–5451) and 2795 mins (range 926–6563). The median GI pH values for the first and second periods, respectively, were: esophageal – 7.0 (range 3.5–7.8) and 4.5 (range 2.9–6.4); gastric – 2.7 (range 1.7–6.2) and 2.0 (range 1.1–3.3); intestinal – 8.2 (range 7.6–8.7) and 7.8 (range 6.7–8.5); first-hour small intestinal – 8.2 (range 7.4–8.7) and 8.3 (range 7.9–8.6); and last-hour large intestinal – 8.5 (range 7.0–8.9) and 7.8 (range 6.3–8.7). Gastric ( P <0.0020) and intestinal pH ( P <0.0059) were significantly increased in the pre-feeding period compared with the post-feeding period. Conclusions and relevance Gastric and intestinal pH differed significantly when the capsule was administered 5 h prior to feeding compared with 1 h after feeding. Transit times for both periods showed high degrees of intra- and inter-individual variability. }, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Telles, Naila J. and Simon, Bradley T. and Scallan, Elizabeth M. and Gould, Emily N. and Papich, Mark G. and He, Yuqing and Lee, Mu-Tien and Lidbury, Jonathan A. and Steiner, Jorg M. and Kathrani, Aarti and et al.}, year={2021}, month={Dec} }
 @article{pusterla_james_bain_barnett_chappell_gaughan_craig_schneider_vaala_papich_2021, title={Investigation of the Bi-Weekly Administration of Diclazuril on the Antibody Kinetics to Sarcocystis Neurona in Healthy Horses}, volume={104}, ISSN={["1542-7412"]}, DOI={10.1016/j.jevs.2021.103713}, abstractNote={The aim of this study was to determine if bi-weekly administration of diclazuril at half the label dose would reduce seroprevalence and magnitude of titers to S. neurona in healthy horses naturally exposed to the apicomplexan protozoal parasite. 12 healthy adult horses were moved from a low-risk exposure to a farm with high exposure rate to S. neurona in their horse population. The horses were randomly assigned to either a treatment or a control group. Treatment consisted in the administration of half the label dose (0.5 mg/kg) of diclazuril (Protazil) pelleted top dress twice weekly (every 3-4 days) for 12 months. Prior to initiation of treatment and monthly thereafter, blood was collected for the detection of antibodies to S. neurona using a quantitative immunoassay. Further, trough plasma diclazuril levels were determined every 60 days. All 20 horses remained healthy during the entire study period. Seroprevalence to S. neurona decreased initially in the treatment group to 50% at 30 days post-treatment commencement. This was followed by a slow increase in seroprevalence in the treatment group before reaching 100% in both groups by 90 days post-treatment commencement. The seroprevalence remained 100% in both groups from 90 to 360 study days. While titer distribution between the two groups was similar at study commencement, treated horses had significantly lower titers throughout the treatment period (P < 0.05). All treated study horses had detectable plasma trough diclazuril levels at the 6 time points and the levels were above the concentration known to inhibit S. neurona in vitro (1.0 ng/mL). The administration of diclazuril pelleted top dress at half the label dose twice weekly was able to maintain low titers to S. neurona in healthy adult horses naturally exposed to the protozoal parasite. Further, trough diclazuril levels were in excess of the minimal concentration known to inhibit S. neurona.}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Pusterla, Nicola and James, Kaitlyn and Bain, Fairfield and Barnett, D. Craig and Chappell, Duane and Gaughan, Earl and Craig, Bryant and Schneider, Chrissie and Vaala, Wendy and Papich, Mark}, year={2021}, month={Sep} }
 @article{papich_narayan_2021, title={Naloxone and nalmefene absorption delivered by hollow microneedles compared to intramuscular injection}, volume={11}, ISSN={["2190-3948"]}, url={https://doi.org/10.1007/s13346-021-01096-0}, DOI={10.1007/s13346-021-01096-0}, abstractNote={Naloxone and nalmefene were administered to seven research beagle dogs (mean weight approximately 12 kg) at doses of 0.04 mg/kg and 0.014 mg/kg for naloxone and nalmefene, respectively. Each dose was administered intramuscularly (IM) with a standard IM injection and with a hollow microneedle device array using needles of 1 mm in length. The IM injection was delivered in the epaxial muscles, and the microneedle injection was delivered in the skin over the shoulder of each dog. Each dog received the same injections in a crossover design. Following the injection, blood samples were collected for plasma analysis of naloxone and nalmefene by high-pressure liquid chromatography with mass spectrometry detection (LCMS). The plasma sample concentrations were plotted for observed patterns of absorption and analyzed with non-compartmental pharmacokinetic methods (NCA). The results showed that the injection of naloxone from the microneedle device produced a higher peak concentration (C MAX ) by 2.15 × compared the IM injection of the same dose, and time to peak concentration (T MAX ) was similar. For the nalmefene injection, the peak was not as high (lower C MAX ) by 0.94 × for the microneedle injection compared to the IM injection of the same dose. The microneedle produced an exposure, measured by area under the curve (AUC), that was 0.85 × and 0.58 × as high for naloxone and nalmefene, respectively, than the injection by the IM route. We also observed that although the dose for naloxone was approximately 3 × higher for naloxone compared to nalmefene, the mean peak concentration achieved from the naloxone injection was more than 12 × higher than that from the nalmefene injection. These studies were designed to test the feasibility of using the hollow microneedle array as an effective method of naloxone and nalmefene delivery for emergency treatment of opioid-induced respiratory depression (OIRD). The results of these studies will form the basis of future studies, using the dog as a model, for development of hollow microneedle microarray devices to deliver opioid antagonists for treatment of OIRD in people.}, journal={DRUG DELIVERY AND TRANSLATIONAL RESEARCH}, publisher={Springer Science and Business Media LLC}, author={Papich, Mark G. and Narayan, Roger J.}, year={2021}, month={Nov} }
 @article{papich_narayan_2021, title={Naloxone and nalmefene absorption delivered by hollow microneedles compared to intramuscular injection}, url={https://doi.org/10.21203/rs.3.rs-933534/v1}, DOI={10.21203/rs.3.rs-933534/v1}, abstractNote={Abstract
        Naloxone and nalmefene were administered to seven research Beagle dogs, (mean weight approximately 12 kg) at a dose of 0.04 mg/kg and 0.014 mg/kg for naloxone and nalmefene, respectively. Each dose was administered intramuscularly (IM) with a standard IM injection and with a hollow microneedle device array using needles of 1 mm in length. The IM injection was delivered in the epaxial muscles, and the microneedle injection was delivered in the skin over the shoulder of each dog. Each dog received the same injections in a cross-over design. Following the injection, blood samples were collected for plasma analysis of naloxone and nalmefene by high pressure liquid chromatography with mass spectrometry detection (LCMS). The plasma sample concentrations were plotted for observed patterns of absorption and analyzed with non-compartmental pharmacokinetic methods (NCA). The results showed that the injection of naloxone from the microneedle device produced a higher peak concentration (CMAX) by 2.15x compared the IM injection of the same dose, and time to peak concentration (TMAX) was similar. For the nalmefene injection, the peak was not as high (lower CMAX) by 0.94x for the microneedle injection compared to the IM injection of the same dose. The microneedle produced an exposure, measured by area under the curve (AUC)) that was 0.85x and 0.58x as high for naloxone and nalmefene, respectively, than the injection by the IM route. We also observed that although the dose for naloxone was approximately 3x higher for naloxone compared to nalmefene, the mean peak concentration achieved from the naloxone injection was more than 12x higher than the nalmefene injection. These studies were designed to test the feasibility of using the hollow microneedle array as an effective method of naloxone and nalmefene delivery for emergency treatment of opioid-induced respiratory depression (OIRD). The results of these studies will form the basis of future studies, using the dog as a model, for development of hollow microneedle microarray devices to deliver opioid antagonists for treatment of OIRD in people.}, author={Papich, Mark G. and Narayan, Roger J.}, year={2021}, month={Sep} }
 @article{zec_papich_oehler_hills_schmid_huth_dodge_pare_2021, title={PHARMACOKINETICS OF A SINGLE ORAL DOSE OF PONAZURIL IN THE INDIAN PEAFOWL (PAVO CRISTATUS)}, volume={52}, ISSN={["1937-2825"]}, DOI={10.1638/2020-0026}, abstractNote={Abstract: Ponazuril, a novel coccidiocidal triazinetrione, has shown promise in addressing apicomplexan diseases in mammals and birds. This study describes the pharmacokinetics of ponazuril in healthy adult Indian peafowl (Pavo cristatus) following a single oral dose administered at two different dosages. Peafowl (four males and four females) were administered compounded ponazuril at 20 or 40 mg/kg orally in a double crossover design, with a 2-wk washout period. Blood was collected from each bird at 2, 4, 8, 24, 48, 72, 96, and 120 h after administration for plasma concentration of ponazuril using high-pressure liquid chromatography. Fecals were evaluated for coccidial shedding for 3 consecutive d prior to the ponazuril trial, 1 wk after the first dose of ponazuril, and 1 wk after the second dose of the trial. After the first trial, one peafowl administered 20 mg/kg ponazuril was shedding coccidia, but no coccidia were detected by the end of the second trial. Ponazuril reached peak concentrations (Tmax) at 21.38 h + 5.25 and 22.04 h + 7.39, and peak concentration (Cmax) were 11.82 µg/ml + 3.01 and 18.42 µg/ml + 4.13, for 20 and 40 mg/kg doses, respectively. Ponazuril was detected at 120 h with a concentration of 9.48 µg/ml + 2.59 and 12.25 µg/ml + 2.89 and a half-life of 219.4 + 58.7 h and 186.7 + 58.7 h, for and 40 mg/kg doses, respectively. Ponazuril in peafowl was well absorbed orally, plasma concentrations increased with dose, and elimination was slower than current dosages for birds would suggest. No obvious adverse effects were observed at either dosage.}, number={2}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Zec, Stephanie H. and Papich, Mark G. and Oehler, David A. and Hills, Kevin and Schmid, Susan and Huth, Ken and Dodge, David M. S. and Pare, Jean A.}, year={2021}, month={Jun}, pages={548–554} }
 @article{field_whoriskey_zhao_papich_2021, title={PHARMACOKINETICS OF SUBCUTANEOUS ALPHA LIPOIC ACID, A PROPOSED THERAPEUTIC AID FOR DOMOIC ACID INTOXICATION IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS)}, volume={52}, ISSN={["1937-2825"]}, DOI={10.1638/2020-0223}, abstractNote={Abstract: Domoic acid (DA) is a potent neurotoxin produced by certain marine algae that can cause neurologic and cardiac dysfunction by activating glutamate receptors. Glutamate receptor overexcitation results in continuous cellular activation, oxidative damage, and cell death. DA toxicosis causes disorientation and seizures, and antiseizure medications are the primary treatment. Alpha lipoic acid (ALA), a powerful antioxidant and glutathione precursor widely used in humans and dogs, can cross the blood-brain barrier to provide antioxidant availability to brain tissue. Hundreds of stranded California sea lions (CSL; Zalophus californianus) are diagnosed annually with DA toxicosis and thus are an appropriate animal in which to establish ALA dosing recommendations for treatment. The objective of this study was to determine the population pharmacokinetics of a single 10- or 20-mg/kg dose of ALA administered subcutaneously into the interscapular region to healthy rehabilitated CSL. Blood was collected at two time points between 15 min and 24 h after administration. Serum ALA concentrations were measured by liquid chromatography-mass spectrometry, and parameters were evaluated using a nonlinear mixed effects model. ALA was rapidly absorbed for each dose, peaking within 20 to 30 minutes, and t1/2 of 40 and 32 min (10 and 20 mg/kg, respectively), followed by an initial steep distribution phase and prolonged elimination phase. Peak concentration (CMAX) was 1,243 ng/ml (10-mg/ml dose) and 5,010 ng/ml (20-mg/ml dose). Serum from 13 CSLd with DA toxicosis treated with 10 mg/kg ALA for 1 to 9 d had measurable levels, and ALA was also measurable in cerebrospinal fluid from two treated CSLs. Therapeutic effects are noted with a CMAX of 4,000 to 5,000 ng/ml in humans; thus in CSLs, 20 mg/kg administered subcutaneously once daily may be sufficient to achieve a therapeutic level in this species. Determination of efficacy and optimal dosing interval and duration require additional investigation.}, number={3}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Field, Cara L. and Whoriskey, Sophie T. and Zhao, Xianguo and Papich, Mark G.}, year={2021}, month={Sep}, pages={872–879} }
 @article{musgrave_hanley_papich_2021, title={POPULATION PHARMACOKINETICS OF CEFTAZIDIME AFTER A SINGLE SUBCUTANEOUS INJECTION AND NORMAL ORAL AND CLOACAL BACTERIAL FLORA SURVEY IN EASTERN HELLBENDERS (CRYPTOBRANCHUS ALLEGANIENSIS ALLEGANIENSIS)}, volume={52}, ISSN={["1937-2825"]}, DOI={10.1638/2020-0145}, abstractNote={Abstract: Population pharmacokinetics utilizing sparse sampling were used to determine pharmacokinetics of ceftazidime in eastern hellbenders (Cryptobranchus alleganiensis alleganiensis) due to their slow growth rate and the limited number of appropriately sized individuals in the zoo-housed population. Twenty-five eastern hellbenders received a single subcutaneous injection of ceftazidime at 20 mg/kg. Each animal had blood samples collected up to four times between 0 and 192 hr postinjection. Plasma samples were analyzed by high-pressure liquid chromatography. A nonlinear mixed-effects model was fitted to the data to determine typical values for population parameters, an ideal method due to the sampling limitation of each hellbender. Results indicate an elimination half-life of 36.63 hr and volume of distribution of 0.31 L/kg. Antibiotic concentrations were above a minimum inhibitory concentration (MIC) value of 8 µg/ml for 120 hr. Prior to antibiotic administration, six hellbenders had oral and six other individuals had cloacal swabs taken for aerobic culture. Fifty-five bacterial isolates were obtained (24 cloacal, 31 oral) with 10/12 (83%) individuals growing three or more different isolates and 11/12 (92%) growing Shewanella putrefaciens. Twelve isolates had susceptibility testing performed and all were susceptible to ceftazidime. These results indicate that ceftazidime is an appropriate choice of antibiotic in hellbenders and when given at a dosage of 20 mg/kg subcutaneously, maintains concentrations above the MIC of susceptible bacteria for up to 5 days.}, number={1}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Musgrave, Kari E. and Hanley, Christopher S. and Papich, Mark G.}, year={2021}, month={Mar}, pages={90–96} }
 @article{goggs_menard_altier_cummings_jacob_lalonde-paul_papich_norman_fajt_scott_et al._2021, title={Patterns of antimicrobial drug use in veterinary primary care and specialty practice: A 6-year multi-institution study}, volume={35}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16136}, DOI={10.1111/jvim.16136}, abstractNote={AbstractBackgroundCombatting antimicrobial resistance requires a One Health approach to antimicrobial stewardship including antimicrobial drug (AMD) use evaluation. Current veterinary AMD prescribing data are limited.ObjectivesTo quantify companion animal AMD prescribing in primary care and specialty practice across 3 academic veterinary hospitals with particular focus on third‐generation cephalosporins, fluoroquinolones, and carbapenems.AnimalsDogs and cats presented to 3 academic veterinary hospitals from 2012 to 2017.MethodsIn this retrospective study, AMD prescribing data from 2012 to 2017 were extracted from electronic medical records at each hospital and prescriptions classified by service type: primary care, specialty practice or Emergency/Critical Care (ECC). Hospital‐level AMD prescribing data were summarized by species, service type, AMD class, and drug. Multivariable logistic full‐factorial regression models were used to estimate hospital, year, species, and service‐type effects on AMD prescribing. Estimated marginal means and confidence intervals were plotted over time.ResultsThe probability of systemic AMD prescribing for any indication ranged between 0.15 and 0.28 and was higher for dogs than cats (P < .05) apart from 2017 at hospital 1. Animals presented to primary care were least likely to receive AMDs (dogs 0.03‐0.15, cats 0.03‐0.18). The most commonly prescribed AMD classes were aminopenicillins/β‐lactamase inhibitors (0.02‐0.15), first‐generation cephalosporins (0.00‐0.09), fluoroquinolones (0.00‐0.04), nitroimidazoles (0.01‐0.06), and tetracyclines (0.00‐0.03). Among the highest priority classes, fluoroquinolones (dogs 0.00‐0.09, cats 0.00‐0.08) and third‐generation cephalosporins (dogs 0.00‐0.04, cats 0.00‐0.05) were most frequently prescribed.Conclusions and Clinical ImportanceAntimicrobial drug prescribing frequencies were comparable to previous studies. Additional stewardship efforts might focus on fluoroquinolones and third‐generation cephalosporins.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, publisher={Wiley}, author={Goggs, Robert and Menard, Julie M. and Altier, Craig and Cummings, Kevin J. and Jacob, Megan E. and Lalonde-Paul, Denise F. and Papich, Mark G. and Norman, Keri N. and Fajt, Virginia R. and Scott, H. Morgan and et al.}, year={2021}, month={May}, pages={1496–1508} }
 @article{gregory_harms_gorges_lewbart_papich_2021, title={Pharmacokinetics of ketorolac in juvenile loggerhead sea turtles (Caretta caretta) after a single intramuscular injection}, volume={44}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/jvp.12952}, DOI={10.1111/jvp.12952}, abstractNote={AbstractKetorolac is a non‐steroidal anti‐inflammatory drug administered as an analgesic in humans. It has analgesic effects comparable to opioids but without adverse effects such as respiratory depression or restrictions because of controlled drug status. We designed this study to examine the potential of ketorolac as an analgesic for sea turtle rehabilitative medicine. Our objective was to determine the pharmacokinetics of a single 0.25 mg/kg intramuscular dose of ketorolac in a population of 16 captive‐raised juvenile loggerhead sea turtles (Caretta caretta). A sparse sampling protocol was utilized, and blood samples were collected for 12 hours after administration of ketorolac. Samples were analyzed with high‐pressure liquid chromatography (HPLC), and a nonlinear mixed effects model (NLME) was used to determine parameters for the population. With these methods, we identified a long elimination half‐life (βT1/2 = 11.867 hr) but a low maximum concentration (CMAX = 0.508 µg/mL) and concentrations were below the level proposed to be therapeutic in humans (EC50 = 0.1–0.3 μg/mL) for most of the collection period. We conclude that ketorolac may not be an appropriate long‐term analgesic for use in loggerhead sea turtles at this dose; however, it may have some benefit as a short‐term analgesic.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Gregory, Taylor M. and Harms, Craig A. and Gorges, Melinda A. and Lewbart, Gregory A. and Papich, Mark G.}, year={2021}, month={Jul}, pages={583–589} }
 @article{houck_papich_delk_2021, title={Phenylbutazone pharmacokinetics in southern white rhinoceros (Ceratotherium simum simum) after oral administration}, volume={12}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/jvp.13036}, DOI={10.1111/jvp.13036}, abstractNote={AbstractSouthern white rhinoceros (Ceratotherium simum simum) frequently develop painful conditions, such as traumatic injuries or osteoarthritis, necessitating the administration of pain‐relieving medications. One of the preferred treatments is the nonsteroidal anti‐inflammatory drug phenylbutazone because of the availability of oral formulations and the familiarity of its use in horses. For the main study, a single oral dose of phenylbutazone at 2 mg/kg was administered to healthy adult rhinoceros (n = 33) housed at six North American zoological institutions. Each rhinoceros had up to four blood samples collected under voluntary behavioural restraint at up to four predetermined time points (0, 1, 1.5, 2, 3, 4, 6, 8, 10, 24, 30 and 48 h). Drug analysis was performed by high‐performance liquid chromatography. The population pharmacokinetic parameters were calculated with nonlinear mixed‐effects modelling, and analysis showed a peak concentration (CMAX) of 3.8 µg/ml at 1.8 h and an elimination half‐life of 9 h. The concentrations achieved were similar to what has been reported for horses and were within the half maximal effective concentration for horses for at least 10 h. A multi‐dose trial in five rhinoceros receiving 2 mg/kg orally once daily for five days found mild accumulation at a predicted factor of 1.2. This study represents the first pharmacokinetic data of phenylbutazone in any rhinoceros species.}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Houck, Emma L. and Papich, Mark G. and Delk, Katie W.}, year={2021}, month={Dec} }
 @article{harms_ruterbories_stacy_christiansen_papich_lynch_barratclough_serrano_2021, title={SAFETY OF MULTIPLE-DOSE INTRAMUSCULAR KETOPROFEN TREATMENT IN LOGGERHEAD TURTLES (CARETTA CARETTA)}, volume={52}, ISSN={["1937-2825"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85103729151&partnerID=MN8TOARS}, DOI={10.1638/2020-0159}, abstractNote={Abstract: Sea turtles are frequently presented for rehabilitation with injuries for which analgesic treatment is warranted. Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) widely used in clinical veterinary medicine for musculoskeletal pain relief. Pharmacokinetics of 2 mg/kg IM have been studied in loggerhead sea turtles (Caretta caretta) as a single and a repeated dose q24hr for 3 days. Safety of longer term administration has not been performed, however, and NSAID use carries a risk of potential complications, including gastrointestinal ulceration, kidney damage, and bleeding. The objective of the current study was to determine the effects of a 5-day course of ketoprofen on thromboelastography (TEG) and hematological (including thrombocytes) and plasma biochemical analytes in loggerheads. A secondary objective was to determine 24-hr trough concentrations of ketoprofen after 5 days of treatment. Eight loggerheads were treated with ketoprofen 2 mg/kg IM q24hr for 5 days, and TEG, hematology, and plasma biochemistry panels were performed before and at the conclusion of treatment. Eight controls were treated with an equivalent volume of saline intramuscularly. Virtually no changes were detected before and after treatment or between treatment and control groups in any of the 24 endpoints evaluated, and marginal differences were not considered clinically relevant. Plasma ketoprofen concentrations after 5 days of treatment indicated no accumulation over that duration. Ketoprofen at 2 mg/kg IM q24hr for up to 5 days in loggerheads appears safe with respect to blood clotting and blood data, although other potential effects were not evaluated.}, number={1}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Harms, Craig A. and Ruterbories, Laura K. and Stacy, Nicole I and Christiansen, Emily F. and Papich, Mark G. and Lynch, Alex M. and Barratclough, Ashley and Serrano, Maria E.}, year={2021}, month={Mar}, pages={126–132} }
 @article{halleran_papich_li_lin_davis_maunsell_riviere_baynes_foster_2022, title={Update on withdrawal intervals following extralabel use of procaine penicillin G in cattle and swine}, volume={260}, ISSN={["1943-569X"]}, DOI={10.2460/javma.21.05.0268}, abstractNote={IntroductionExtralabel drug use (ELDU) is defined as the use of an FDA-approved medication in a manner that differs from what is provided on the label of the medication.1 Administration of the medication to a different species or at a different dose, volume, route, duration, indication, or frequency than indicated on the label is considered ELDU. Extralabel drug use also requires an extended withdrawal period to avoid violative residues, and practitioners can get advice on withdrawal intervals (WDIs) following ELDU from the Food Animal Residue Avoidance and Depletion Program (FARAD). Penicillin is one of the most commonly used}, number={1}, journal={Journal of the American Veterinary Medical Association}, author={Halleran, J.L. and Papich, M.G. and Li, M. and Lin, Z. and Davis, J. and Maunsell, F. and Riviere, J. and Baynes, R. and Foster, D.M.}, year={2022}, month={Jan}, pages={50–55} }
 @article{papich_2021, title={Antimicrobial agent use in small animals what are the prescribing practices, use of PK‐PD principles, and extralabel use in the United States?}, url={https://doi.org/10.1111/jvp.12921}, DOI={10.1111/jvp.12921}, abstractNote={AbstractIn this review, the availability and deficiencies of current antimicrobial agents for companion animals in the United States are described. Although several active agents are FDA‐approved for small animals, there are many unmet needs. These needs are greatest for cats, for the treatment of antibiotic drug‐resistant infections, and to treat new or emerging pathogens that were not considered on older labels. The older agents approved before 1997 are often outdated, unavailable, or have inaccurate labeling. Subsequently, veterinarians treat dogs and cats with many unapproved antimicrobial agents that are licensed for human use. Although these drugs may be effective, there are also concerns that this use can produce drug‐resistant bacteria that may be a public health risk. Although this concern is real, there is also evidence that any antimicrobial use in small animals can produce resistant fecal bacteria and stewardship principles should aim at reducing any unnecessary antibiotic use. This could be accomplished by avoiding some of the older, ineffective, or outdated agents described in this paper. There is a need for incentives to approve new agents that will be more appropriate for treating infections in companion animals without increasing the risk of drug‐resistant bacteria that could potentially be transferred to humans and the environment and create a public health risk.}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Papich, Mark G.}, year={2021}, month={Mar} }
 @article{tolbert_spencer_lynch_papich_lidbury_2020, title={Capsule endoscopy detects insufficient treatment of gastric bleeding in a dog with chronic hepatitis}, volume={8}, ISSN={["2052-6121"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85094609210&partnerID=MN8TOARS}, DOI={10.1136/vetreccr-2020-001238}, abstractNote={A five‐year‐old dog was presented for a chronic non‐regenerative anaemia, copper‐associated chronic hepatitis and suspected portal hypertension. The anaemia was suspected to be from gastrointestinal (GI) bleeding and persisted despite chronic omeprazole treatment (1.1 mg/kg orally every 12 hours). Capsule endoscopy confirmed severe gastric bleeding. A pH capsule was orally administered to evaluate the efficacy of gastric acid suppressant treatment. The mean gastric pH of the dog over the three‐hour monitoring period was 4.7, and the percentage time that the intragastric pH were ≥3 and 4 were 100 per cent and 99 per cent, respectively. Substantial upper GI bleeding persisted despite excellent gastric acid suppression, bringing into question the value of routinely recommending such therapy in dogs with hepatic failure without additional monitoring for adequacy of treatment.}, number={4}, journal={VETERINARY RECORD CASE REPORTS}, author={Tolbert, M. Katherine and Spencer, Ashley and Lynch, Alex M. and Papich, Mark G. and Lidbury, Jonathan A.}, year={2020}, month={Oct} }
 @article{banovic_denley_blubaugh_scheibe_lemo_papich_2020, title={Effect of diphenhydramine and cetirizine on immediate and late-phase cutaneous allergic reactions in healthy dogs: a randomized, double-blinded crossover study}, volume={31}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12840}, abstractNote={BackgroundCurrently, there is insufficient evidence to confirm oral diphenhydramine (DPH) efficacy to prevent mast cell degranulation and histamine release in dogs.Hypothesis/ObjectiveTo determine and compare the effects oral of DPH and cetirizine on the immediate‐ and late‐phase cutaneous allergic reactions in healthy dogs.AnimalsTwelve healthy laboratory beagle dogs.Methods and materialsThe study was designed as a randomized, double‐blinded crossover study in which each dog served as its own control; twice‐daily oral DPH (2.2 mg/kg) or cetirizine (2 mg/kg) were given for six days with a two week washout period. Intradermal injections of histamine, compound 48/80 (positive control) and saline (negative control) were performed on the right thorax 10 days before drug administration (baseline), during oral antihistamine administration on Day 6 and 10 days after last medication dosage. Global wheal scores (GWS) at 20 min and late‐phase reactions (LPR) at 6 h post‐injection were evaluated by an investigator blinded to the drug and the interventions.ResultsTreatment with cetirizine significantly reduced histamine and compound 48/80 GWS and LPR compared to baseline; there was no significant difference for DPH. In all dogs, oral DPH and cetirizine reached plasma concentrations considered therapeutic in people. No adverse effect or behavioural changes were observed during the study.Conclusion and clinical significanceIn conclusion, oral cetirizine was effective in preventing cutaneous allergic reactions without any obvious adverse effects in dogs. Oral DPH failed to show an inhibitory effect despite attaining plasma drug concentrations that are considered effective in people.}, number={4}, journal={VETERINARY DERMATOLOGY}, author={Banovic, Frane and Denley, Tara and Blubaugh, Amanda and Scheibe, Ileia and Lemo, Niksa and Papich, Mark G.}, year={2020}, month={Aug}, pages={256-+} }
 @article{traverson_stewart_papich_2020, title={Evaluation of bioabsorbable calcium sulfate hemihydrate beads for local delivery of carboplatin}, volume={15}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0241718}, DOI={10.1371/journal.pone.0241718}, abstractNote={The objectives of this study were to evaluate a novel kit of resorbable calcium sulfate beads marketed specifically for use in veterinary medicine and generally used for local delivery of antimicrobials as carboplatin-delivery system. The study characterized the elution of carboplatin in vitro, and investigated whether the initial dose and formulation of carboplatin, or the bead size significantly influences carboplatin elution in vitro. Calcium sulfate hemihydrate beads of 3- and 5-mm diameter were prepared. Five doses and two formulations of carboplatin (20, 50, 100, and 500 mg carboplatin per kit in powder formulation; 20 mg in liquid formulation) were tested in triplicates for each diameter beads. Beads were placed in 37°C phosphate buffered saline for 72 hours. Carboplatin concentrations in the eluent were measured by high-performance liquid chromatography at 11 time points with a modified United States Pharmacopeia assay. Concentrations of carboplatin in the eluent proportionally increased with the initial dose and peaked between 13 and 52 hours, ranging from 42.1% to 79.3% of the incorporated load. Higher peak concentrations, percentages released, and elution rates were observed with the liquid formulation and with higher carboplatin doses. There was no significant difference in maximum carboplatin concentrations between 3- and 5-mm diameter beads, but 5-mm diameter beads had slower elution rates. The novel kit can be used for preparation of carboplatin-impregnated resorbable calcium sulfate beads at variable doses, sizes and formulations. Further study is warranted to define the in vivo requirements and effective carboplatin dose, spatial diffusion and desired duration of elution.}, number={11}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Traverson, Marine and Stewart, Connor E. and Papich, Mark G.}, editor={Clegg, SimonEditor}, year={2020}, month={Nov}, pages={e0241718} }
 @article{kukanich_woodruff_bieberly_papich_kukanich_2021, title={Evaluation of urine concentrations of amoxicillin and clavulanate in cats}, url={https://doi.org/10.1111/jvim.15991}, DOI={10.1111/jvim.15991}, abstractNote={AbstractBackgroundTo characterize urinary isolates, the Clinical and Laboratory Standards Institute (CLSI) uses an amoxicillin breakpoint for cats based on plasma (not urine) drug concentrations (≤0.25 μg/mL), but a urine‐specific breakpoint for dogs exists (≤8 μg/mL).ObjectivesTo measure urine concentrations of amoxicillin and clavulanate after PO administration of amoxicillin‐clavulanate to cats, and to suggest updated urine‐specific susceptibility breakpoints for PO amoxicillin and amoxicillin‐clavulanate in cats.AnimalsEleven healthy purpose‐bred cats.MethodsCats were given 3 62.5 mg doses of amoxicillin‐clavulanate PO q12h. After the third dose, urine was collected over 28 hours, recording urination time and volume. At least 3 urine samples were collected per cat. Liquid chromatography with mass spectrometry was used to determine the urine concentrations of amoxicillin and clavulanate.ResultsAmoxicillin concentrations were >8 μg/mL in all urine samples collected within 12 hours after administration (range, 31.6‐1351 μg/mL), with means of 929 μg/mL (0‐6 hours) and 532 μg/mL (6‐12 hours). The mean half‐life of amoxicillin in urine was 1.99 hours, and mean recovery was 30%. Clavulanate was detected in all urine samples, with mean half‐life of 2.17 hours.Conclusions and Clinical ImportanceOrally administered amoxicillin‐clavulanate resulted in urine amoxicillin concentrations above the cutoff (8 μg/mL) for wild‐type Escherichia coli in all cats. Because urine‐specific susceptibility testing breakpoints can be determined using urine concentrations, this information should allow new CLSI uropathogen susceptibility breakpoints for amoxicillin and amoxicillin‐clavulanate in healthy cats, increasing the urine breakpoint from ≤0.25 to ≤8 μg/mL.}, journal={Journal of Veterinary Internal Medicine}, author={KuKanich, Kate and Woodruff, Kallie and Bieberly, Zackery and Papich, Mark G. and KuKanich, Butch}, year={2021}, month={Jan} }
 @misc{patel_thomson_alby_babady_culbreath_galas_lockhart_lubbers_morgan_richter_et al._2020, title={Expert Opinion on Verification of Antimicrobial Susceptibility Tests}, volume={58}, ISSN={["1098-660X"]}, DOI={10.1128/JCM.00945-20}, abstractNote={On behalf of the Clinical and Laboratory Standards Institute (CLSI), the Expert Panel on Microbiology would like to respond to the recent commentary by Kirby and colleagues voicing concerns related to verification of commercial antimicrobial susceptibility testing (AST) for new drugs that are introduced into the clinical laboratory (1).….}, number={11}, journal={JOURNAL OF CLINICAL MICROBIOLOGY}, author={Patel, Jean B. and Thomson, Richard B. and Alby, Kevin and Babady, Esther and Culbreath, Karissa and Galas, Marcelo F. and Lockhart, Shawn R. and Lubbers, Brian V. and Morgan, Margie and Richter, Sandra S. and et al.}, year={2020}, month={Nov} }
 @article{van wick_papich_hashem_dominguez-villegas_2020, title={PHARMACOKINETICS OF A SINGLE DOSE OF FLURALANER ADMINISTERED ORALLY TO AMERICAN BLACK BEARS (URSUS AMERICANUS)}, volume={51}, ISSN={["1937-2825"]}, DOI={10.1638/2019-0200}, abstractNote={Abstract: Sarcoptic mange continues to impact free-ranging mammal populations, including the American black bear (Ursus americanus). Administration of a single oral dose of fluralaner may be a viable treatment option for captive and free-ranging black bears affected by mange. This novel ectoparasitic in the isoxazoline class acts as an inhibitor of γ-aminobutyric acid (GABA)-gated chloride channels and l-glutamate–gated chloride channels (GluCls) and is commercially available in the United States as a flea and tick preventative medication for domestic dogs and cats. Pharmacokinetic parameters of fluralaner were evaluated in clinically healthy American black bear cubs (n = 10) administered a single oral dose of fluralaner at a targeted minimum dose of 25 mg/kg. Blood was collected at 24 hr and 7, 14, 21, 28, 35, 42, 49, 56, 63, and 70 days, and harvested plasma was analyzed for drug concentration using high-performance liquid chromatography. The average half-life (Ke t 1/2) was determined to be 4.9 days, which is shorter than that published in domestic dogs. It was estimated that the average drug withdrawal time is approximately 64–72 days in this species.}, number={3}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Van Wick, Peach and Papich, Mark G. and Hashem, Brie and Dominguez-Villegas, Ernesto}, year={2020}, month={Sep}, pages={691–695} }
 @article{greene_mylniczenko_storms_burns_lewbart_byrd_papich_2020, title={Pharmacokinetics of Ketoprofen in Nile Tilapia (Oreochromis niloticus) and Rainbow Trout (Oncorhynchus mykiss)}, volume={7}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2020.585324}, abstractNote={The objective of this study was to document the pharmacokinetics of ketoprofen following 3 mg/kg intramuscular (IM) and intravenous (IV) injections in rainbow trout (Oncorhynchus mykiss) and 8 mg/kg intramuscular (IM) injection in Nile tilapia (Oreochromis niloticus). Plasma was collected laterally from the tail vein for drug analysis at various time intervals up to 72 h following the injection of ketoprofen. In trout, area under the curve (AUC) levels were 115.24 μg hr/mL for IM and 135.69 μg hr/mL for IV groups with a half-life of 4.40 and 3.91 h, respectively. In both trout and tilapia, there were detectable ketoprofen concentrations in most fish for 24 h post-injection. In tilapia, there was a large difference between the R- and S-enantiomers, suggesting either chiral inversion from R- to S-enantiomer or more rapid clearance of the R-enantiomer. AUC values of the S- and R-enantiomers were 510 and 194 μg hr/Ml, respectively, corresponding to a faster clearance for the R-enantiomer. This study shows that there were very high plasma concentrations of ketoprofen in trout and tilapia with no adverse effects observed. Future studies on the efficacy, frequency of dosing, analgesia, adverse effects, and route of administration are warranted.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Greene, Whitney and Mylniczenko, Natalie D. and Storms, Timothy and Burns, Charlene M. and Lewbart, Gregory A. and Byrd, Lynne and Papich, Mark G.}, year={2020}, month={Oct} }
 @article{papich_2021, title={Pharmacokinetics of doxycycline in dogs}, url={https://doi.org/10.1111/jvp.12941}, DOI={10.1111/jvp.12941}, abstractNote={Journal of Veterinary Pharmacology and TherapeuticsVolume 44, Issue 3 p. 419-419 LETTER TO THE EDITOR Pharmacokinetics of doxycycline in dogs Mark G. Papich, Corresponding Author Mark G. Papich mark_papich@ncsu.edu orcid.org/0000-0002-7591-7898 North Carolina State University, Raleigh, NC, USA Correspondence Mark G. Papich, North Carolina State University, Raleigh, NC, USA. Email: mark_papich@ncsu.eduSearch for more papers by this author Mark G. Papich, Corresponding Author Mark G. Papich mark_papich@ncsu.edu orcid.org/0000-0002-7591-7898 North Carolina State University, Raleigh, NC, USA Correspondence Mark G. Papich, North Carolina State University, Raleigh, NC, USA. Email: mark_papich@ncsu.eduSearch for more papers by this author First published: 24 December 2020 https://doi.org/10.1111/jvp.12941Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume44, Issue3May 2021Pages 419-419 RelatedInformation}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Papich, Mark G.}, year={2021}, month={May} }
 @article{scott_field_papich_harms_2020, title={Plasma concentrations of itraconazole following a single oral dose in juvenile California sea lions (Zalophus californianus)}, url={https://doi.org/10.1111/jvp.12865}, DOI={10.1111/jvp.12865}, abstractNote={AbstractThe objective of this study was to establish a single‐dose pharmacokinetic profile for orally administered itraconazole in California sea lions (Zalophus californianus). Twenty healthy rehabilitated juvenile California sea lions were included in this study. Itraconazole capsules were administered orally with food at a target dose of 5–10 mg/kg. Blood samples were collected from each animal at 0 hr and at two of the following timepoints: 0.5, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hr. Quantitative analysis of itraconazole in plasma samples was performed by high‐performance liquid chromatography. An average maximum concentration of 0.22 µg/ml ± 0.11 was detected 4 hr after administration. The average concentration fell to 0.12 µg/ml ± 0.11 by 6 hr and 0.02 µg/ml ± 0.02 at 12 hr. At no point did concentrations reach 0.5 µg/ml, the concentration commonly accepted for therapeutic efficacy. While this formulation was well tolerated by the sea lions, oral absorption was poor and highly variable among individuals. These data indicate that a single oral dose of itraconazole given as a capsule at 5–10 mg/kg, under the conditions used in this study, does not achieve therapeutic plasma concentrations in California sea lions.}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Scott, Gregory and Field, Cara L. and Papich, Mark G. and Harms, Craig A.}, year={2020}, month={Jul} }
 @article{griffioen_lewbart_papich_2020, title={Population pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in clinically diseased or injured Eastern box turtles (Terrapene carolina carolina), yellow‐bellied sliders (Trachemys scripta scripta), and river cooters (Pseudemys concinna)}, url={https://doi.org/10.1111/jvp.12843}, DOI={10.1111/jvp.12843}, abstractNote={AbstractEnrofloxacin is frequently administered to turtles in wildlife clinics during rehabilitation due to its wide spectrum of antibacterial activity and availability of injectable formulations. However, sufficient pharmacokinetic data to guide dosing are lacking. The objective of this study was to determine pharmacokinetic parameters of enrofloxacin and its active metabolite, ciprofloxacin, in chelonians presenting injured to a wildlife clinic. Thirty‐six Eastern box turtles (EBT, Terrapene carolina carolina), 23 yellow‐bellied sliders (YBS, Trachemys scripta scripta), and 13 river cooters (RC, Pseudemys concinna) received a single subcutaneous injection of enrofloxacin at 10 mg/kg. Blood samples were collected between 0 and 240 hr postinjection. Pharmacokinetic parameters were determined using nonlinear mixed‐effects modeling (NMLE). Overall elimination half‐life (T½) was over 75 hr, and varied among species. T½ was 63 hr in EBT and 79 hr in YBS, which is longer than in previous reports. The volume of distribution (steady‐state) was 1.4 L/kg across turtle species, but highly variable—ranging from 0.4 L/kg in RC to 1.9 L/kg in YBS. Antibiotic concentrations were above a minimum inhibitory concentration value of 0.5 µg/ml for over 200 hr. These results indicate variable pharmacokinetic parameters for enrofloxacin among turtle species, which will help guide appropriate dosing protocols in injured turtles.}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Griffioen, John A. and Lewbart, Gregory A. and Papich, Mark G.}, year={2020}, month={Mar} }
 @article{zalesak_sanchez_pich_papich_2020, title={Preliminary Pilot Study of Itraconazole After a Single Oral Dose of a Veterinary Formulation Solution in African Penguins (Spheniscus demersus)}, volume={34}, ISSN={["1938-2871"]}, DOI={10.1647/1082-6742-34.1.52}, abstractNote={Abstract: Aspergillosis is a common cause of morbidity and mortality in captive penguins. Itraconazole, an antifungal drug, is commonly used to treat aspergillosis infections in avian species; however, commercially available human formulations are costly, and studies have shown the effectiveness of compounded formulations to be unreliable. The US Food and Drug Administration (FDA) recently approved a veterinary formulation of itraconazole, Itrafungol, for use in cats. This study provides preliminary results from limited sampling evaluating whether this veterinary formulation is suitable for future studies in the African penguin (Spheniscus demersus). A 20 mg/kg PO itraconazole dose was administered to 9 African penguins. Blood samples were taken over the course of 24 hours; each sample was collected from a different bird to minimize stress to the animals. Plasma was analyzed by high-performance liquid chromatography for concentrations of itraconazole. The drug was absorbed in all penguins, and plasma concentrations in 5 of 9 penguins (56%) were found to be greater than the established therapeutic dose of 1.0 µg/ mL. To our knowledge, this is the first study that has investigated a 20 mg/kg dose of itraconazole in a penguin species. The small sample size limits the conclusions that can be drawn from this preliminary study. Nonetheless, we demonstrate encouraging evidence that the FDA-approved formulation of oral itraconazole solution should be considered for future study as a cost-effective treatment for aspergillosis in African penguins and other avian species.}, number={1}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Zalesak, Selina M. and Sanchez, Carlos R. and Pich, Ashley A. and Papich, Mark G.}, year={2020}, month={Mar}, pages={52–56} }
 @article{jones_gaier_enomoto_ishii_pilla_price_suchodolski_steiner_papich_messenger_et al._2020, title={The effect of combined carprofen and omeprazole administration on gastrointestinal permeability and inflammation in dogs}, url={https://doi.org/10.1111/jvim.15897}, DOI={10.1111/jvim.15897}, abstractNote={AbstractBackgroundProton pump inhibitors (eg, omeprazole) commonly are administered concurrently with nonsteroidal anti‐inflammatory drugs (NSAIDs; eg, carprofen) as prophylaxis to decrease the risk of gastrointestinal (GI) injury. However, evidence to support this practice is weak, and it might exacerbate dysbiosis and inflammation.Hypothesis/ObjectivesTo evaluate the effect of carprofen alone or combined with omeprazole in dogs. We hypothesized that coadministration of omeprazole and carprofen would significantly increase GI permeability and dysbiosis index (DI) compared to no treatment or carprofen alone.AnimalsSix healthy adult colony beagle dogs.MethodsGastrointestinal permeability and inflammation were assessed by serum lipopolysaccharide (LPS) concentration, plasma iohexol concentration, fecal DI, and fecal calprotectin concentration in a prospective, 3‐period design. In the first 7‐day period, dogs received no intervention (baseline). During the 2nd period, dogs received 4 mg/kg of carprofen q24h PO for 7 days. In the 3rd period, dogs received 4 mg/kg of carprofen q24h and 1 mg/kg of omeprazole q12h PO for 7 days. Gastrointestinal permeability testing was performed at the end of each period. Data were analyzed using repeated measures mixed model analysis of variance with Tukey‐Kramer post hoc tests (P < .05).ResultsSerum LPS and plasma iohexol concentrations did not differ between treatments. Fecal calprotectin concentrations differed between treatments (P = .03). The DI varied over time based on the treatment received (P = .03). Coadministration of omeprazole and carprofen significantly increased fecal calprotectin concentration and DI compared to baseline and carprofen alone.Conclusions and Clinical ImportanceOmeprazole prophylaxis induces fecal dysbiosis and increases intestinal inflammatory markers when coadministered with carprofen to otherwise healthy dogs with no other risk factors for GI bleeding.}, journal={Journal of Veterinary Internal Medicine}, author={Jones, Susan M. and Gaier, Ann and Enomoto, Hiroko and Ishii, Patricia and Pilla, Rachel and Price, Josh and Suchodolski, Jan and Steiner, Joerg M. and Papich, Mark G. and Messenger, Kristen and et al.}, year={2020}, month={Sep} }
 @article{chumbler_schildt_mawby_papich_2020, title={Use of intravenous lipid therapy in a cat with carprofen overdose}, volume={8}, ISSN={["2050-0904"]}, DOI={10.1002/ccr3.2772}, abstractNote={AbstractIntravenous lipid emulsion (ILE) was administered to a cat with no adverse effects. This case report postulates that ILE can be used for the treatment of carprofen toxicity in cats and supports the lipid sink theory as the main mechanism of action.}, number={4}, journal={CLINICAL CASE REPORTS}, author={Chumbler, Nathan S. and Schildt, Julie C. and Mawby, Diane I. and Papich, Mark G.}, year={2020}, month={Apr}, pages={653–657} }
 @article{von dollen_jones_beachler_harris_papich_lyle_bailey_2019, title={Antimicrobial Activity of Ceftiofur and Penicillin With Gentamicin Against Escherichia coli and Streptococcus equi Subspecies zooepidemicus in an Ex Vivo Model of Equine Postpartum Uterine Disease}, volume={79}, ISSN={["1542-7412"]}, DOI={10.1016/j.jevs.2019.06.005}, abstractNote={The use of antimicrobials for the management of equine uterine disease is commonplace, with antibiotic selection generally based on empirical evidence or in vitro sensitivity results. However, the potential disconnect between these laboratory results and clinical efficacy in the mare raises concern for antibiotic failure and subsequent development of resistant organisms. In this work, we attempt to bridge this gap by using an ex vivo model of the equine postpartum uterus to quantitatively evaluate the antimicrobial activity of two commonly used antibiotic treatments in the mare (ceftiofur and penicillin with gentamicin). The activity of both of these treatments was evaluated in two different fluid environments (standard bacterial culture broth and equine postpartum uterine fluid) against clinical isolates of E. coli and S. zooepidemicus. Although treatment with ceftiofur was effective at reducing growth of S. zooepidemicus in equine postpartum uterine fluid, it did not reduce bacterial growth of E. coli. Treatment with procaine penicillin G with gentamicin achieved at least bacteriostatic activity against E. coli in both fluid types, and bactericidal activity against S. zooepidemicus in both fluid types. The intrauterine infusion of procaine penicillin G with gentamicin in cases of postpartum uterine disease caused by E. coli or S. zooepidemicus is supported by the results of this work.}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Von Dollen, Karen A. and Jones, Monica and Beachler, Theresa and Harris, Tonya L. and Papich, Mark G. and Lyle, Sara K. and Bailey, C. Scott}, year={2019}, month={Aug}, pages={121–126} }
 @article{foster_jacob_farmer_callahan_theriot_kathariou_cernicchiaro_prange_papich_2019, title={Ceftiofur formulation differentially affects the intestinal drug concentration, resistance of fecal Escherichia coli, and the microbiome of steers}, volume={14}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0223378}, abstractNote={Antimicrobial drug concentrations in the gastrointestinal tract likely drive antimicrobial resistance in enteric bacteria. Our objective was to determine the concentration of ceftiofur and its metabolites in the gastrointestinal tract of steers treated with ceftiofur crystalline-free acid (CCFA) or ceftiofur hydrochloride (CHCL), determine the effect of these drugs on the minimum inhibitory concentration (MIC) of fecal Escherichia coli, and evaluate shifts in the microbiome. Steers were administered either a single dose (6.6 mg/kg) of CCFA or 2.2 mg/kg of CHCL every 24 hours for 3 days. Ceftiofur and its metabolites were measured in the plasma, interstitium, ileum and colon. The concentration and MIC of fecal E. coli and the fecal microbiota composition were assessed after treatment. The maximum concentration of ceftiofur was higher in all sampled locations of steers treated with CHCL. Measurable drug persisted longer in the intestine of CCFA-treated steers. There was a significant decrease in E. coli concentration (P = 0.002) within 24 hours that persisted for 2 weeks after CCFA treatment. In CHCL-treated steers, the mean MIC of ceftiofur in E. coli peaked at 48 hours (mean MIC = 20.45 ug/ml, 95% CI = 10.29–40.63 ug/ml), and in CCFA-treated steers, mean MIC peaked at 96 hours (mean MIC = 10.68 ug/ml, 95% CI = 5.47–20.85 ug/ml). Shifts in the microbiome of steers in both groups were due to reductions in Firmicutes and increases in Bacteroidetes. CCFA leads to prolonged, low intestinal drug concentrations, and is associated with decreased E. coli concentration, an increased MIC of ceftiofur in E. coli at specific time points, and shifts in the fecal microbiota. CHCL led to higher intestinal drug concentrations over a shorter duration. Effects on E. coli concentration and the microbiome were smaller in this group, but the increase in the MIC of ceftiofur in fecal E. coli was similar.}, number={10}, journal={PLOS ONE}, author={Foster, Derek M. and Jacob, Megan E. and Farmer, Kyle A. and Callahan, Benjamin J. and Theriot, Casey M. and Kathariou, Sophia and Cernicchiaro, Natalia and Prange, Timo and Papich, Mark G.}, year={2019}, month={Oct} }
 @article{ehling_baeumer_papich_2019, title={Diphenhydramine pharmacokinetics after oral and intravenous administration of diphenhydramine and oral administration of dimenhydrinate to healthy dogs, and pharmacodynamic effect on histamine-induced wheal formation: a pilot study}, volume={30}, ISSN={["1365-3164"]}, DOI={10.1111/vde.12727}, abstractNote={BackgroundHistamine type‐1 (H1) receptor antagonists such as diphenhydramine are frequently used for treatment of pruritus in dogs, yet therapeutic efficacy for allergic disorders is reported to be highly variable. Dimenhydrinate is a salt of diphenhydramine and 8‐chlorotheophylline, and has been reported to produce superior oral absorption of diphenhydramine.Hypothesis/ObjectiveTo determine the pharmacokinetic and pharmacodynamic properties of diphenhydramine in dogs after intravenous (1 mg/kg) and oral (5 mg/kg) administration, and when given orally as dimenhydrinate at a dose of 10 mg/kg (≈5 mg/kg diphenhydramine).AnimalsEach drug was administered to six healthy, fasted mixed‐breed dogs in a research facility, using a cross‐over design.Methods and materialsBlood samples were collected for pharmacokinetic analysis of diphenhydramine and chlorotheophylline at defined intervals. Pharmacodynamic response was measured by histamine‐mediated cutaneous wheal formation.ResultsThere was great variability in the data and one dog was an extreme outlier. The mean systemic availabilities of diphenhydramine were 7.8% and 22.0% after oral administration of diphenhydramine and dimenhydrinate, respectively, whereas the mean maximum concentrations were 36 (± 20) and 124 (± 46) ng/mL. The terminal elimination half‐lives of diphenhydramine and dimenhydrinate were 5.0 (± 7.1) and 11.6 (± 17.7) h, respectively. Plasma diphenhydramine concentrations did not correlate with the percentage reduction in histamine‐induced wheal formation. Theophylline reached plasma concentrations considered to be therapeutic for dogs.ConclusionOral absorption of diphenhydramine was approximately three times greater with a longer half‐life when it was administered as the combination product dimenhydrinate.}, number={2}, journal={VETERINARY DERMATOLOGY}, author={Ehling, Sarah and Baeumer, Wolfgang and Papich, Mark G.}, year={2019}, month={Apr}, pages={91-+} }
 @article{mason_papich_schmale_harms_davis_2019, title={Enrofloxacin Pharmacokinetics and Sampling Techniques in California Sea Hares (Aplysia californica)}, volume={58}, ISSN={1559-6109}, url={http://dx.doi.org/10.30802/AALAS-JAALAS-18-000072}, DOI={10.30802/AALAS-JAALAS-18-000072}, abstractNote={This pharmacokinetic study was designed to determine the pharmacokinetics of enrofloxacin at 5 mg/kg when given to sea hares in their hemolymph. Enrofloxacin is a commonly used antimicrobial in veterinary medicine and potentially could be used to treat sea hares exposed to susceptible
 bacterial species. We individually identified 8 juvenile Aplysia californica and group housed them in an open seawater flow system at 14 to 18 °C; 2 served as untreated controls. The remaining 6 animals were injected into the hemocoel with 0.030 mL of 22.7 mg/mL enrofloxacin (average
 dose, 5 to 6 mg/kg). At each time point, 300 μL hemolymph was collected from the pedal hemolymph sinus and HPLC-analyzed for enrofloxacin and ciprofloxacin levels. Enrofloxacin was detected in all dosed animals, at an average peak concentration of 3 μg/mL in hemolymph, and remained in
 the body for 20.3 h with an average clearance of 0.19 μg × h/mL. No ciprofloxacin was detected in any Aplysia in this study. Hemocoel injection appears to be an effective way to administer enrofloxacin to Aplysia and reach clinically relevant concentrations. Enrofloxacin reached therapeutic target concentrations in A. californica when dosed according to the regimen described in the current report.}, number={2}, journal={Journal of the American Association for Laboratory Animal Science}, publisher={American Association for Laboratory Animal Science}, author={Mason, Sharon E and Papich, Mark G and Schmale, Michael C and Harms, Craig A and Davis, Sally A}, year={2019}, month={Mar}, pages={231–234} }
 @article{weese_blondeau_boothe_guardabassi_gumley_papich_jessen_lappin_rankin_westropp_et al._2019, title={International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats}, volume={247}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2019.02.008}, abstractNote={Urinary tract disease is a common clinical presentation in dogs and cats, and a common reason for antimicrobial prescription. This document is a revision and expansion on the 2011 Antimicrobial Use Guidelines for Treatment of Urinary Tract Disease in Dogs and Cats, providing recommendations for diagnosis and management of sporadic bacterial cystitis, recurrent bacterial cystitis, pyelonephritis, bacterial prostatitis, and subclinical bacteriuria. Issues pertaining to urinary catheters, medical dissolution of uroliths and prophylaxis for urological procedures are also addressed.}, journal={VETERINARY JOURNAL}, author={Weese, J. Scott and Blondeau, Joseph and Boothe, Dawn and Guardabassi, Luca G. and Gumley, Nigel and Papich, Mark and Jessen, Lisbeth Rem and Lappin, Michael and Rankin, Shelley and Westropp, Jodi L. and et al.}, year={2019}, month={May}, pages={8–25} }
 @article{madsen_messenger_papich_2019, title={Pharmacokinetics of levofloxacin following oral administration of a generic levofloxacin tablet and intravenous administration to dogs}, volume={80}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.80.10.957}, abstractNote={Abstract

OBJECTIVE
To determine the pharmacokinetics of levofloxacin following oral administration of a generic levofloxacin tablet and IV administration to dogs and whether the achieved plasma levofloxacin concentration would be sufficient to treat susceptible bacterial infections.


ANIMALS
6 healthy adult Beagles.


PROCEDURES
Levofloxacin was administered orally as a generic 250-mg tablet (mean dose, 23.7 mg/kg) or IV as a solution (15 mg/kg) to each dog in a crossover study design, with treatments separated by a minimum 2-day washout period. Blood samples were collected at various points for measurement of plasma levofloxacin concentration via high-pressure liquid chromatography. Pharmacokinetic analysis was performed with compartmental modeling.


RESULTS
After oral administration of the levofloxacin tablet, mean (coefficient of variation) peak plasma concentration was 15.5 μg/mL (23.8%), mean elimination half-life was 5.84 hours (20.0%), and mean bioavailability was 104% (29.0%). After IV administration, mean elimination half-life (coefficient of variation) was 6.23 hours (14.7%), systemic clearance was 145.0 mL/kg/h (22.2%), and volume of distribution was 1.19 L/kg (17.1%).


CONCLUSIONS AND CLINICAL RELEVANCE
In these dogs, levofloxacin was well absorbed when administered orally, and a dose of approximately 25 mg/kg was sufficient to reach pharmacokinetic-pharmacodynamic targets for treating infections with susceptible Enterobacteriaceae (ie, ≤ 0.5 μg/mL) or Pseudomonas aeruginosa (ie, ≤ 1 μg/mL) according to clinical breakpoints established by the Clinical and Laboratory Standards Institute.
}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Madsen, Melanie and Messenger, Kristen and Papich, Mark G.}, year={2019}, month={Oct}, pages={957–962} }
 @article{bailey_sheldon_allender_papich_chinnadurai_2019, title={Pharmacokinetics of orally administered tramadol in Muscovy ducks (Cairina moschata domestica)}, volume={1}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12743}, DOI={10.1111/jvp.12743}, abstractNote={AbstractThis study documents the pharmacokinetics of oral tramadol in Muscovy ducks. Six ducks received a single 30 mg/kg dose of tramadol, orally by stomach tube, with blood collection prior to and up to 24 hr after tramadol administration. Plasma tramadol, and metabolites O‐desmethyltramadol (M1), and N,O‐didesmethyltramadol (M5) concentrations were determined by high‐pressure liquid chromatography (HPLC) with fluorescence (FL) detection. Pharmacokinetic parameters were calculated using a one‐compartment model with first‐order input. No adverse effects were noted after oral administration. All ducks achieved plasma concentrations of tramadol above 0.10 μg/ml and maintained those concentrations for at least 12 hr. Elimination half‐life was 3.95 hr for tramadol in ducks, which is similar to other avian species. All ducks in this study produced the M1 metabolite and maintained plasma concentrations above 0.1 μg/ml for at least 24 hr.}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Bailey, Ryan S. and Sheldon, Julie D. and Allender, Matthew C. and Papich, Mark G. and Chinnadurai, Sathya K.}, year={2019}, month={Jan} }
 @article{donnelly_papich_zirkelbach_norton_szivek_burkhalter_impellizeri_stacy_2019, title={Plasma Bleomycin Concentrations during Electrochemotherapeutic Treatment of Fibropapillomas in Green Turtles Chelonia mydas}, volume={31}, ISSN={["1548-8667"]}, DOI={10.1002/aah.10067}, abstractNote={AbstractFibropapillomatosis of sea turtles is traditionally treated with surgical debulking techniques that are often associated with prolonged healing and tumor recurrence. Electrochemotherapy was recently described for green turtles Chelonia mydas and can be an alternative to surgery and even general anesthesia. The objectives of this study were to replicate an electrochemotherapy protocol from a previous report and add plasma bleomycin analysis to the treatment. After bleomycin injection into similarly sized tumors of two green turtles and immediate electroporation at two time points, plasma bleomycin reached detectable concentrations that were considerably lower than those found in human studies. At 3 months posttherapy, no healing complications or recurrences were encountered and only scar tissue remained. This study adds further support that electrochemotherapy with bleomycin has the potential to be used as an effective alternative treatment for this complex disease.}, number={2}, journal={JOURNAL OF AQUATIC ANIMAL HEALTH}, author={Donnelly, Kyle A. and Papich, Mark G. and Zirkelbach, Bette and Norton, Terry and Szivek, Anna and Burkhalter, Brooke and Impellizeri, Joseph A. and Stacy, Nicole I.}, year={2019}, month={Jun}, pages={186–192} }
 @article{schmitt_nollens_simeone_papich_2019, title={Population Pharmacokinetics of Danofloxacin After Single Intramuscular Dose Administration in California Brown Pelicans (Pelecanus occidentalis californicus)}, volume={33}, ISSN={["1938-2871"]}, DOI={10.1647/2018-366}, abstractNote={Abstract: The pharmacokinetics of danofloxacin was investigated in rehabilitated California brown pelicans (Pelecanus occidentalis californicus) after a single intramuscular injection at a dose of 15 mg/kg body weight. The concentration of the drug in plasma was assayed by high-pressure liquid chromatography. A sparse-sampling design was used to reduce the number of samples (1–4 venipunctures) obtained from 24 brown pelicans. A population pharmacokinetic analysis with nonlinear mixed-effects modeling was used to accommodate the sparse-sampling strategy. The nonlinear mixed-effects modeling approach measured both fixed effects (typical values for the population) and random effects (between-subject variability) for this population. A 1-compartment model best represented the concentration-versus-time data after injection. After injection, the elimination half-life, peak concentration, area under the curve, and volume of distribution were 2.76 hours, 2.5 µg/mL, 13.75 µg/h/mL, and 4.35 L/kg, respectively. Rate of absorption was highly variable among the birds. The intramuscular injection of danofloxacin in pelicans at this dose produced plasma concentrations that meet therapeutic targets for bacteria with a minimum inhibitory concentration of ≤0.25 µg/mL. This dose can be used for future studies to evaluate the efficacy of danofloxacin for treating susceptible bacteria.}, number={4}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Schmitt, Todd L. and Nollens, Hendrik H. and Simeone, Claire A. and Papich, Mark G.}, year={2019}, month={Dec}, pages={361–368} }
 @article{martinez_el-kattan_awji_papich_2019, title={Reconciling Human-Canine Differences in Oral Bioavailability: Looking beyond the Biopharmaceutics Classification System}, volume={21}, ISSN={["1550-7416"]}, DOI={10.1208/s12248-019-0364-4}, abstractNote={The extrapolation of oral bioavailability (F) information between dogs and humans has had an important role in the drug development process, whether it be to support an assessment of potential human pharmaceutical formulations or to identify the bioavailability challenges that may be encountered in dogs. Accordingly, these interspecies extrapolations could benefit from a tool that helps identify those drug characteristics consistent with species similarities in F. Our initial effort to find such a tool led to an exploration of species differences as it pertained to the biopharmaceutics classification system (BCS). However, using a range of compounds, we concluded that solubility and permeability alone could not explain interspecies inconsistencies in estimates of F. Therefore, we have now extended our evaluation to include canine versus human comparisons of F based upon the biopharmaceutics drug disposition classification system (BDDCS) and the extended clearance classification system (ECCS). Using the same data as that in our initial BCS assessments, we conclude that although neither the BDDCS nor the ECCS can reliably improve our ability to determine when F will be similar in humans and dogs, the ECCS provides a mechanism to help define possible causes for observed human-canine inconsistencies.}, number={5}, journal={AAPS JOURNAL}, author={Martinez, Marilyn N. and El-Kattan, Ayman and Awji, Elias and Papich, Mark}, year={2019}, month={Aug} }
 @article{adin_kurtz_atkins_papich_vaden_2019, title={Role of electrolyte concentrations and renin‐angiotensin‐aldosterone activation in the staging of canine heart disease}, volume={34}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/jvim.15662}, DOI={10.1111/jvim.15662}, abstractNote={AbstractBackgroundRefractory congestive heart failure (CHF) and associated diuretic resistance are not well defined.ObjectivesTo characterize renal function, electrolyte concentrations, indices of diuretic efficacy, and renin‐angiotensin‐aldosterone system (RAAS) activation in dogs with naturally occurring heart disease (HD) in American College of Veterinary Internal Medicine stages B1, B2, C, and D and to determine their usefulness in defining HD stages.AnimalsGroup 1:149 dogs with HD stages B1, B2, C, and D. Group 2:22 dogs with HD stages C and D.MethodsGroup 1: Renal parameters, serum and urine electrolyte and diuretic concentrations, and urine aldosterone concentrations were measured. Medication dosages and measured variables were compared among stages. Correlation of furosemide dosages to serum concentrations was explored. Group 2: Angiotensin‐converting enzyme activity and RAAS components were measured and compared among CHF stages.ResultsSerum chloride concentration was the best differentiator of HD stage. Furosemide PO dosages (≤6 mg/kg/day) were weakly correlated with serum furosemide concentrations, whereas higher dosages were not significantly correlated. Angiotensin‐converting enzyme inhibitor dosage and RAAS inhibition were greater in stage D, compared to stage C dogs.Conclusions and Clinical ImportanceHypochloremia is a useful marker for stage D HD in dogs. Poor furosemide dosage correlation to serum concentration may indicate variable and poor absorption, especially at higher dosages, advanced disease, or both. A small number of stage D dogs met proposed criteria for diuretic resistance. Greater RAAS inhibition in stage D versus stage C indicates effectiveness of RAAS‐suppressive treatments in this group of dogs with refractory CHF.}, number={1}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Adin, Darcy and Kurtz, Kari and Atkins, Clarke and Papich, Mark G. and Vaden, Shelly}, year={2019}, month={Nov}, pages={53–64} }
 @inbook{papich_2018, place={Hoboken, New Jersey, USA.}, edition={10th}, title={ Immunosuppressive Drugs}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, M.G.}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={1226–1244} }
 @article{acierno_brown_coleman_jepson_papich_stepien_syme_2018, title={ACVIM consensus statement: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats}, volume={32}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.15331}, DOI={10.1111/jvim.15331}, abstractNote={An update to the 2007 American College of Veterinary Internal Medicine (ACVIM) consensus statement on the identification, evaluation, and management of systemic hypertension in dogs and cats was presented at the 2017 ACVIM Forum in National Harbor, MD. The updated consensus statement is presented here. The consensus statement aims to provide guidance on appropriate diagnosis and treatment of hypertension in dogs and cats.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, publisher={Wiley}, author={Acierno, Mark J. and Brown, Scott and Coleman, Amanda E. and Jepson, Rosanne E. and Papich, Mark and Stepien, Rebecca L. and Syme, Harriet M.}, year={2018}, pages={1803–1822} }
 @article{marks_kook_papich_tolbert_willard_2018, title={ACVIM consensus statement: Support for rational administration of gastrointestinal protectants to dogs and cats}, volume={32}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.15337}, DOI={10.1111/jvim.15337}, abstractNote={The gastrointestinal (GI) mucosal barrier is continuously exposed to noxious toxins, reactive oxygen species, microbes, and drugs, leading to the development of inflammatory, erosive, and ultimately ulcerative lesions. This report offers a consensus opinion on the rational administration of GI protectants to dogs and cats, with an emphasis on proton pump inhibitors (PPIs), histamine type‐2 receptor antagonists (H2RAs), misoprostol, and sucralfate. These medications decrease gastric acidity or promote mucosal protective mechanisms, transforming the management of dyspepsia, peptic ulceration, and gastroesophageal reflux disease. In contrast to guidelines that have been established in people for the optimal treatment of gastroduodenal ulcers and gastroesophageal reflux disease, effective clinical dosages of antisecretory drugs have not been well established in the dog and cat to date. Similar to the situation in human medicine, practice of inappropriate prescription of acid suppressants is also commonplace in veterinary medicine. This report challenges the dogma and clinical practice of administering GI protectants for the routine management of gastritis, pancreatitis, hepatic disease, and renal disease in dogs and cats lacking additional risk factors for ulceration or concerns for GI bleeding. Judicious use of acid suppressants is warranted considering recent studies that have documented adverse effects of long‐term supplementation of PPIs in people and animals.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, publisher={Wiley}, author={Marks, Stanley L. and Kook, Peter H. and Papich, Mark G. and Tolbert, M. K. and Willard, Michael D.}, year={2018}, pages={1823–1840} }
 @inbook{papich_riviere_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={Aminoglycoside Antibiotics}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, MG and Riviere, JE}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={877–902} }
 @inbook{papich_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={Anticoagulant, Antiplatelet, and Hemostatic Drugs}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, M.G.}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={625–646} }
 @inbook{papich_2018, place={Hoboken, New Jersey}, edition={10th}, title={Anticonvulsant Drugs}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, M.G.}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={395–415} }
 @inbook{papich_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={Chloramphenicol and Derivatives, Macrolides, Lincosamides, and Miscellaneous Antimicrobials}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, M.G.}, editor={Riviere, JE and Papich, MGEditors}, year={2018} }
 @article{mawby_whittemore_fowler_papich_2018, title={Comparison of absorption characteristics of oral reference and compounded itraconazole formulations in healthy cats}, volume={252}, ISSN={["1943-569X"]}, DOI={10.2460/javma.252.2.195}, abstractNote={Abstract
OBJECTIVE To compare absorption characteristics of orally administered compounded itraconazole capsules and suspension with those of reference (brand-name) formulations in healthy cats.
DESIGN Randomized crossover study.
ANIMALS 8 healthy adult cats.
PROCEDURES After 12 hours of food withholding, cats received 50 mg of itraconazole (reference capsule, reference solution, compounded capsule, and compounded suspension) in a randomized crossover design, with a 21-day washout period. Capsules were administered with a small meal. Blood samples were collected at predetermined intervals for high-pressure liquid chromatography analysis of plasma itraconazole concentrations. Area under the concentration-time curve, maximum concentration, and terminal half-life of itraconazole were determined and compared among formulations.
RESULTS 7 cats completed the study. Mean half-life of itraconazole in reference formulations was 18 to 26 hours. Absorption of the reference solution was 3 times that of the reference capsule. Compounded formulations were absorbed poorly and inconsistently. Complete pharmacokinetic results for the compounded capsule were obtained for only 3 of 6 cats and for the compounded suspension for only 1 of 5 cats, precluding bioequivalence analysis. Relative absorption of compounded formulations was only 2% to 8% of reference formulation values.
CONCLUSIONS AND CLINICAL RELEVANCE Compounded oral formulations of itraconazole should not be used for cats because of poor absorption. The differences in absorption between the 2 reference formulations suggested that doses required to meet human target serum concentrations in cats are markedly different (capsules, 12.5 mg/kg [5.7 mg/lb], q 24 h, with food; solution, 4 mg/kg [1.8 mg/lb], q 24 h, without food).}, number={2}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Mawby, Dianne I. and Whittemore, Jacqueline C. and Fowler, Leanne E. and Papich, Mark G.}, year={2018}, month={Jan}, pages={195–200} }
 @article{hunyadi_papich_pusterla_2018, title={Diclazuril nonlinear mixed-effects pharmacokinetic modelling of plasma concentrations after oral administration to adult horses every 3-4 days}, volume={242}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2018.10.009}, abstractNote={The purpose of this study was to determine if a low dose of diclazuril (0.5mg/kg of 1.56% diclazuril pellets) given to six healthy adult horses every 3-4 days for a total of five administrations would achieve steady-state plasma concentrations known to be inhibitory to Sarcocystis neurona and Neospora caninum. Blood was collected via venipuncture immediately before (trough concentrations) and 10h after (peak concentrations) each diclazuril administration and analysed by high-pressure liquid chromatography. The mean population-derived peak concentration was 0.284μg/mL and the mean terminal half-life was 1.6 days, but with a large variation. Thus, low dose diclazuril pellets produce steady-state plasma drug concentrations known to inhibit S. neurona (0.001μg/mL) and N. caninum (0.1μg/mL).}, journal={VETERINARY JOURNAL}, author={Hunyadi, Laszlo and Papich, Mark G. and Pusterla, Nicola}, year={2018}, month={Dec}, pages={74–76} }
 @article{ferguson_jacob_theriot_callahan_prange_papich_foster_2018, title={Dosing Regimen of Enrofloxacin Impacts Intestinal Pharmacokinetics and the Fecal Microbiota in Steers}, volume={9}, ISSN={1664-302X}, url={http://dx.doi.org/10.3389/fmicb.2018.02190}, DOI={10.3389/fmicb.2018.02190}, abstractNote={Objective: The intestinal concentrations of antimicrobial drugs that select for resistance in fecal bacteria of cattle are poorly understood. Our objective was to associate active drug concentrations in the intestine of steers with changes in the resistance profile and composition of the fecal microbiome. Methods: Steers were administered either a single dose (12.5 mg/kg) or 3 multiple doses (5 mg/kg) of enrofloxacin subcutaneously every 24 h. Enrofloxacin and ciprofloxacin concentrations in intestinal fluid were measured over 96 h, and the abundance and MIC of E. coli in culture and the composition of the fecal microbiota by 16S rRNA gene sequencing were assessed over 192 h after initial treatment. Results: Active drug concentrations in the ileum and colon exceeded plasma and interstitial fluid concentrations, but were largely eliminated by 48 h after the last dose. The concentration of E. coli in the feces significantly decreased during peak drug concentrations, but returned to baseline by 96 h in both groups. The median MIC of E. coli isolates increased for 24 h in the single dose group, and for 48 h in the multiple dose group. The median MIC was higher in the multiple dose group when compared to the single dose group starting 12 h after the initial dose. The diversity of the fecal microbiota did not change in either treatment group, and taxa-specific changes were primarily seen in phyla commonly associated with the rumen. Conclusions: Both dosing regimens of enrofloxacin achieve high concentrations in the intestinal lumen, and the rapid elimination mitigates long-term impacts on fecal E. coli resistance and the microbiota.}, journal={Frontiers in Microbiology}, publisher={Frontiers Media SA}, author={Ferguson, Kaitlyn M. and Jacob, Megan E. and Theriot, Casey M. and Callahan, Benjamin J. and Prange, Timo and Papich, Mark G. and Foster, Derek M.}, year={2018}, month={Sep} }
 @inbook{gruen_sherman_papich_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={Drugs Affecting Animal Behavior}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Gruen, M.E. and Sherman, BL and Papich, M.G.}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={416–448} }
 @inbook{papich_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={Drugs for Treating Gastrointestinal Diseases}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, M.G.}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={1245–1277} }
 @inbook{papich_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={Drugs that Affect the Respiratory System}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, M.G.}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={1302–1320} }
 @article{krull_thomovsky_chen_mealey_papich_2019, title={Evaluation of Transdermal Administration of Phenobarbital in Healthy Cats}, volume={55}, ISSN={["1547-3317"]}, DOI={10.5326/JAAHA-MS-6670}, abstractNote={ABSTRACT
               The purpose was to determine the safety and achievable serum concentrations of transdermally administered phenobarbital in healthy cats. The hypothesis was that transdermal phenobarbital would achieve therapeutic serum concentrations (15–45 µg/mL) with minimal short-term adverse effects. Enrolled cats had normal physical and neurologic exams and unremarkable bloodwork. Transdermal phenobarbital in a pluronic lecithin organogel–based vehicle was administered at a dosage of 3.0–3.1 mg/kg per ear pinna (total of 6.0–6.2 mg/kg) every 12 hr for 14 days. Serum phenobarbital concentrations were measured 3–6 hr after dosing at seven different times over 15 days. The mean and median serum concentration of phenobarbital at study completion were 5.57 and 4.08 µg/mL, respectively. Mean peak concentration and mean time to peak concentration were 5.94 µg/mL and 13.3 days, respectively. Mild adverse effects were observed. Potency was analyzed in three replicates of the transdermal phenobarbital gel administered; potencies ranged from 62.98 to 82.02%. Transdermal application of phenobarbital in healthy cats achieves a detectable, but subtherapeutic, serum concentration and appears safe in the short term. The use of therapeutic drug monitoring is recommended when this formulation of phenobarbital is used to ensure therapeutic serum concentrations are achieved.}, number={1}, journal={JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION}, author={Krull, Daniel P. and Thomovsky, Stephanie Ann and Chen, Annie Vivian and Mealey, Katrina L. and Papich, Mark G.}, year={2019}, pages={1–7} }
 @inbook{papich_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={Fluoroquinolone Antimicrobial Drugs}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, M.G.}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={953–987} }
 @inbook{kukanich_papich_2018, place={Hoboken, New Jersey}, edition={10th}, title={Opioid Analgesic Drugs}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={KuKanich, B and Papich, MG}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={281–323} }
 @article{adin_atkins_papich_2018, title={Pharmacodynamic assessment of diuretic efficacy and braking in a furosemide continuous infusion model}, volume={20}, ISSN={["1875-0834"]}, url={https://doi.org/10.1016/j.jvc.2018.01.003}, DOI={10.1016/j.jvc.2018.01.003}, abstractNote={{"Label"=>"INTRODUCTION", "NlmCategory"=>"BACKGROUND"} Diuretic failure is a potential life-ending event but is unpredictable and poorly understood. The objectives of this study were to evaluate pharmacodynamic markers of furosemide-induced diuresis and to investigate mechanisms of diuretic braking in dogs receiving constant rate infusion (CRI) of furosemide. {"Label"=>"ANIMALS", "NlmCategory"=>"METHODS"} Six healthy male dogs. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} Raw data and stored samples from one arm of a previously published study were further analyzed to mechanistically investigate causes of diuretic braking in these dogs. Urine volume was recorded hourly during a 5-h furosemide CRI. Urine and blood samples were collected hourly to measure serum and urine electrolytes, urine aldosterone, and plasma and urine furosemide. Serum electrolyte fractional excretion was calculated. Urine sodium concentration was indexed to urine potassium (uNa:uK) and urine furosemide (uNa:uFur) concentrations, plasma furosemide concentration was indexed to urine furosemide concentration (pFur:uFur), and urine aldosterone was indexed to urine creatinine (UAldo:C). Temporal change and the relationship to urine volume were evaluated for these measured and calculated variables. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} Urine volume was significantly correlated with urine electrolyte amounts and with uNa:uK. The ratio of pFur:uFur decreased during the infusion, whereas furosemide excretion was unchanged. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} There was a strong relationship between urine volume and absolute urine electrolyte excretion. Urine volume was strongly correlated to uNa:uK, giving it potential as a spot indicator of urine production during diuresis. The decrease in uNa:uK over time during the infusion is consistent with mineralocorticoid modification of urinary electrolyte excretion, supporting renin-angiotensin-aldosterone activation as a cause of diuretic braking in this model.}, number={2}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, publisher={Elsevier BV}, author={Adin, D. and Atkins, C. and Papich, M. G.}, year={2018}, month={Apr}, pages={92–101} }
 @article{serpa_brooks_diverse_ness_birschmann_papich_stokol_2018, title={Pharmacokinetics and Pharmacodynamics of an Oral Formulation of Apixaban in Horses After Oral and Intravenous Administration}, volume={5}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2018.00304}, abstractNote={Horses with inflammatory and infectious disorders are often treated with injectable heparin anticoagulants to prevent thrombotic complications. In humans, a new class of direct oral acting anticoagulants (DOAC) appear as effective as heparin, while eliminating the need for daily injections. Our study in horses evaluated apixaban, a newly approved DOAC for human thromboprophylaxis targeting activated factor X (Xa). Our goals were to: (1) Determine pharmacokinetics and pharmacodynamics of apixaban after oral (PO) and intravenous (IV) administration in horses; (2) Detect any inhibitory effects of apixaban on ex vivo Equid herpesvirus type 1 (EHV-1)-induced platelet activation, and (3) Compare an anti-Xa bioactivity assay with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) for measuring apixaban concentrations. In a blinded placebo-controlled cross-over study, five horses received a single dose (0.2 mg/kg) of apixaban or placebo PO or IV. Blood was collected before and at 3 (IV) or 15 (PO) min, 30 and 45 min, and 1, 2, 3, 4, 6, 8, and 24 h after dosing for measuring apixaban UPLC-MS concentrations and anti-Xa activity. Pharmacodynamic response was measured in a dilute prothrombin time (dPT) assay. Flow cytometric EHV-1-induced platelet P-selectin expression and clinical pathologic safety testing were performed at baseline, 2 and 24 h and baseline and 24 h, respectively. We found no detectable apixaban in plasma PO administration. After IV administration, plasma apixaban levels followed a two-compartment model, with concentrations peaking at 3 min and decreasing to undetectable levels by 8 h. The elimination half-life was 1.3 ± 0.2 h, with high protein binding (92–99%). The dPT showed no relationship to apixaban UPLC-MS concentration and apixaban did not inhibit EHV-1-induced platelet activation after IV dosing. Apixaban anti-Xa activity showed excellent correlation to UPLC-MS (r2 = 0.9997). Our results demonstrate that apixaban has no apparent clinical utility as an anticoagulant for horses due to poor oral availability.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Serpa, Priscila B. S. and Brooks, Marjory B. and Diverse, Thomas and Ness, Sally and Birschmann, Ingyild and Papich, Mark G. and Stokol, Tracy}, year={2018}, month={Dec} }
 @article{sleeper_o’donnell_fitzgerald_papich_2018, title={Pharmacokinetics of furosemide after intravenous, oral and transdermal administration to cats}, ISSN={1098-612X 1532-2750}, url={http://dx.doi.org/10.1177/1098612x18805879}, DOI={10.1177/1098612x18805879}, abstractNote={Objectives The aim of this study was to determine the pharmacokinetics of furosemide in cats following intravenous (IV), oral and transdermal administration. Methods This study used six healthy adult cats in a three-phase design to compare plasma furosemide concentrations in cats that received one IV 2 mg/kg dose of furosemide, one oral 2 mg/kg dose of furosemide and 3 days of q12h dosing with 2 mg/kg furosemide transdermally applied to the ear pinna. Results After IV administration the elimination half-life was (mean and coefficient of variation) 2.25 h (72%), systemic clearance was 149 ml/kg/h (27.4%) and volume of distribution was 227 ml/kg (22%). After oral administration the terminal half-life was 1.2 h (18.7%), peak concentration was 3.4 μg/ml (51.7%) and bioavailability was 48.4%. The transdermal plasma concentrations were undetectable or very low at most time points, and pharmacokinetics were not determined from the transdermal dose. Conclusions and relevance Furosemide was rapidly eliminated in cats after oral and IV administration and is probably best administered orally at least q12h in cats with heart failure. The oral dose absorbed was approximately 50%, but the absorption from transdermal administration was negligible. }, journal={Journal of Feline Medicine and Surgery}, publisher={SAGE Publications}, author={Sleeper, Meg M and O’Donnell, Patricia and Fitzgerald, Caitlin and Papich, Mark G}, year={2018}, month={Oct}, pages={1098612X1880587} }
 @article{cerreta_masterson_lewbart_dise_papich_2018, title={Pharmacokinetics of ketorolac in wild Eastern box turtles (Terrapene carolina carolina
) after single intramuscular administration}, volume={11}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12733}, DOI={10.1111/jvp.12733}, abstractNote={AbstractKetorolac is a nonsteroidal anti‐inflammatory drug that possesses potent analgesic activity comparable to morphine. The opioid shortage in the United States has led to an unreliable supply of opioids for use in rehabilitation facilities, thus underscoring the need for research on the safe and effective use of nonopioid alternatives. The goal of this study was to determine the pharmacokinetics of ketorolac after a single 0.25 mg/kg intramuscular injection administered to injured Eastern box turtles (Terrapene carolina carolina). A sparse blood sampling protocol was used to collect samples from 32 wild turtles that presented to the Turtle Rescue Team at North Carolina State University for traumatic injuries. Blood was collected from 0 to 24 hr after injection and analyzed via high‐pressure liquid chromatography (HPLC). A nonlinear mixed‐effects (NLME) model was fitted to the data to obtain typical values for population parameters. Using this approach, we identified a long half‐life (T1/2) of 9.78 hr and a volume of distribution (Vss) of 0.26 L/kg. We have concluded that this long T1/2 for a dose of 0.25 mg/kg ketorolac‐injected IM provides plasma levels above a previously published target level for 24‐hour analgesia to allow for once daily dosing.}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Cerreta, Anthony J. and Masterson, Chris A. and Lewbart, Gregory A. and Dise, Delta R. and Papich, Mark G.}, year={2018}, month={Nov} }
 @article{cerreta_lewbart_dise_papich_2018, title={Population pharmacokinetics of ceftazidime after a single intramuscular injection in wild turtles}, volume={41}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12500}, DOI={10.1111/jvp.12500}, abstractNote={Ceftazidime, a third‐generation cephalosporin, is important for treating opportunistic bacterial infections in turtles. Antibacterial dosage regimens are not well established for wild turtles and are often extrapolated from other reptiles or mammals. This investigation used a population pharmacokinetic approach to study ceftazidime in wild turtles presented for rehabilitation. Ceftazidime was administered to 24 wild turtles presented to the Turtle Rescue Team at North Carolina State University. A sparse blood sampling protocol was used to collect samples from 0 to 120 hr with three samples per individual after injection. Plasma samples were analyzed by high‐pressure liquid chromatography (HPLC). A nonlinear mixed‐effects model (NLME) was fitted to the data to determine typical values for population parameters. We identified a long half‐life (T½) of approximately 35 hr and volume of distribution (VSS) of 0.26 L/kg. We concluded that this long T½ will allow for a dose of 20 mg/kg injected IM to maintain concentrations above the MIC of most wild‐type bacteria for 5 days. Because of long intervals between injections, stability of stored formulations was measured and showed that 90% strength was maintained for 120 hr when stored in the refrigerator and for 25 days when stored in the freezer.}, number={4}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Cerreta, A. J. and Lewbart, G. A. and Dise, D. R. and Papich, M. G.}, year={2018}, month={Mar}, pages={495–501} }
 @article{muñana_otamendi_nettifee_papich_2018, title={Population pharmacokinetics of extended-release levetiracetam in epileptic dogs when administered alone, with phenobarbital or zonisamide}, volume={32}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.15298}, DOI={10.1111/jvim.15298}, abstractNote={BackgroundExtended‐release levetiracetam (LEV‐XR) has gained acceptance as an antiepileptic drug in dogs. No studies have evaluated its disposition in dogs with epilepsy.Hypothesis/ObjectivesTo evaluate the pharmacokinetics of LEV‐XR in epileptic dogs when administered alone or with phenobarbital or zonisamide.AnimalsEighteen client‐owned dogs on steady‐state maintenance treatment with LEV‐XR (Group L, n = 6), LEV‐XR and phenobarbital (Group LP, n = 6), or LEV‐XR and zonisamide (Group LZ, n = 6).MethodsPharmacokinetic study. Blood samples were collected at 0, 2, 4, 8, and 12 hours after LEV‐XR was administered with food. Plasma LEV concentrations were determined by high‐pressure liquid chromatography. A population pharmacokinetic approach and nonlinear mixed effects modeling were used to analyze the data.ResultsTreatment group accounted for most of the interindividual variation. The LP group had lower CMAX (13.38 μg/mL) compared to the L group (33.01 μg/mL) and LZ group (34.13 μg/mL), lower AUC (134.86 versus 352.95 and 452.76 hours·μg/mL, respectively), and higher CL/F (0.17 versus 0.08 and 0.07 L/kg/hr, respectively). The half‐life that defined the terminal slope of the plasma concentration versus time curve (~5 hours) was similar to values previously reported for healthy dogs.Conclusions and Clinical ImportanceConsiderable variation exists in the pharmacokinetics of LEV‐XR in dogs with epilepsy being treated with a common dose regimen. Concurrent administration of phenobarbital contributed significantly to the variation. Other factors evaluated, including co‐administration of zonisamide, were not shown to contribute to the variability. Drug monitoring may be beneficial to determine the most appropriate dose of LEV‐XR in individual dogs.}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Muñana, Karen R. and Otamendi, Arturo J. and Nettifee, Julie A. and Papich, Mark G.}, year={2018}, month={Sep}, pages={1677–1683} }
 @article{sanchez_zalesak_pich_papich_2019, title={Population pharmacokinetics of itraconazole solution after a single oral administration in captive lesser flamingos (Phoeniconaias minor)}, volume={42}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12721}, abstractNote={AbstractAspergillosis is an infectious, non‐contagious fungal disease of clinical importance in flamingo collections. Itraconazole is an antifungal drug commonly used in the treatment and prophylaxis of avian aspergillosis. Studies have shown that dosage regimes in birds vary based on different itraconazole presentation and administration methods. This investigation used a population pharmacokinetic approach to study itraconazole in lesser flamingos. Itraconazole was administered orally at 10 mg/kg to 17 flamingos. A sparse blood sampling was performed on the subjects, and samples were collected at 1, 2, 3, 5, 8, 12, 16, 21, and 24 hr post‐drug administration. Twelve flamingos were sampled three times, three birds bled twice and two sampled once. Itraconazole in plasma was quantified using high‐pressure liquid chromatography (HPLC). A one‐compartment pharmacokinetic model with first order absorption was fitted to the data using nonlinear mixed effects modeling (NLME) to determine values for population parameters. We identified a long half‐life (T½) of more than 75 hr and a maximum plasma concentration (CMAX) of 1.69 µg/ml, which is above the minimal inhibitory concentrations for different aspergillus isolates. We concluded that plasma drug concentrations of itraconazole were maintained in a population of flamingos above 0.5 ug/ml for at least 24 hr after a single oral dose of 10 mg/kg of itraconazole solution.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Sanchez, Carlos R. and Zalesak, Selina and Pich, Ashley A. and Papich, Mark G.}, year={2019}, month={Jan}, pages={1–6} }
 @inbook{papich_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={Sulfonamides and Potentiated Sulfonamides}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, M.G.}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={796–825} }
 @inbook{papich_riviere_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={Tetracycline Antibiotics}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, MG and Riviere, JE}, editor={Riviere, JE and Papich, MGEditors}, year={2018} }
 @article{pastina_early_bergman_nettifee_maller_bray_waldron_castel_munana_papich_et al._2018, title={The pharmacokinetics of cytarabine administered subcutaneously, combined with prednisone, in dogs with meningoencephalomyelitis of unknown etiology}, volume={41}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/jvp.12667}, DOI={10.1111/jvp.12667}, abstractNote={AbstractThe objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50 mg/m2 as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360 min after administration. All dogs were concurrently receiving prednisone (0.5–2 mg kg−1day−1). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed‐effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8 μg/ml. The population estimate (CV%) for elimination half‐life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0 μg/ml at the 30‐, 60‐, 90‐, and 120‐min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50 mg/m2 SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs.}, number={5}, journal={Journal of Veterinary Pharmacology & Therapeutics}, publisher={Wiley}, author={Pastina, B. and Early, P.J. and Bergman, R.L. and Nettifee, J. and Maller, A. and Bray, K.Y. and Waldron, R.J. and Castel, A.M. and Munana, K.R. and Papich, M.G. and et al.}, year={2018}, month={Oct}, pages={638–643} }
 @article{adrian_papich_baynes_stafford_lascelles_2018, title={The pharmacokinetics of gabapentin in cats}, volume={32}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.15313}, DOI={10.1111/jvim.15313}, abstractNote={BackgroundGabapentin is the most commonly prescribed medication for the treatment of chronic musculoskeletal pain in cats. Despite this common and chronic usage, clinically relevant pharmacokinetic data is lacking.ObjectivesTo evaluate the pharmacokinetics of clinically relevant dosing regimens of gabapentin in cats.AnimalsEight research‐purpose mixed‐breed cats.MethodsCats were enrolled in a serial order, non‐randomized pharmacokinetic study. Gabapentin was administered as an IV bolus (5 mg/kg), orally (10 mg/kg) as a single dose or twice daily for 2 weeks, or as a transdermal gel (10 mg/kg) in serial order. Serial blood samples were collected up to 48 hours. Plasma concentrations were determined using Ultra Performance Liquid Chromatography‐Mass Spectrometry. Compartmental analysis was used to generate gabapentin time‐concentration models.ResultsAfter IV administration CL (median (range)) and terminal half‐life were 160.67 mL/kg*hr (119.63‐199.11) and 3.78 hours (3.12‐4.47), respectively. The oral terminal half‐life was 3.63 hours (2.96‐4.77), and 3.72 hours (3.12‐4.51) for single and repeated dosing. TMAX and CMAX, as predicted by the model were 1.05 hours (0.74‐2.11), and 12.42 μg/mL (8.31‐18.35) after single oral dosing, and 0.77 hours (0.58‐1.64), and 14.78 μg/mL (9.70‐18.41) after repeated oral dosing. Bioavailability after a single oral dose was 94.77% (82.46‐122.83).ImportanceRepeated oral dosing of gabapentin did not alter the drug's pharmacokinetics, making dose adjustments unnecessary with long‐term treatment. As prepared, the transdermal route is an inappropriate choice for drug administration. These relevant data are important for future studies evaluating potential efficacy of the medication for treating chronic pain states in cats.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, publisher={Wiley}, author={Adrian, Derek and Papich, Mark G. and Baynes, Ronald and Stafford, Emma and Lascelles, B. Duncan X.}, year={2018}, pages={1996–2002} }
 @book{je_mg_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={Veterinary Pharmacology and Therapeutics}, publisher={Wiley Blackwell. John Wiley & Sons}, year={2018} }
 @inbook{riviere_papich_2018, place={Hoboken, New Jersey}, edition={10th}, title={Veterinary Pharmacology: An Introduction to the Discipline}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Riviere, JE and Papich, MG}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={3–7} }
 @inbook{davidson_papich_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={Veterinary Pharmacy}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Davidson, G and Papich, MG}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={1427–1438} }
 @inbook{papich_2018, place={Hoboken, New Jersey, USA}, edition={10th}, title={β-Lactam Antibiotics: Penicillins, Cephalosporins, and Related Drugs}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, M.G.}, editor={Riviere, JE and Papich, MGEditors}, year={2018}, pages={826–857} }
 @inbook{papich_2017, place={St. Louis, Missouri}, edition={Eighth}, title={Antibacterial Drug Therapy}, booktitle={Textbook of Veterinary Internal Medicine: Disease of the Dog and the Cat}, publisher={Elsevier}, author={Papich, M.G.}, editor={Ettinger, S.J. and Feldman, E.C. and Côté, E.Editors}, year={2017}, pages={683–687} }
 @inbook{papich_2017, place={St. Louis, Missouri}, edition={Eighth}, title={Antifungal and antiviral therapy}, booktitle={Textbook of Veterinary Internal Medicine: Disease of the Dog and the Cat}, publisher={Elsevier}, author={Papich, M.G.}, editor={Ettinger, S.J. and Feldman, E.C. and Côté , E.Editors}, year={2017}, pages={688–692} }
 @article{lappin_blondeau_boothe_breitschwerdt_guardabassi_lloyd_papich_rankin_sykes_turnidge_et al._2017, title={Antimicrobial use Guidelines for Treatment of Respiratory Tract Disease in Dogs and Cats: Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases}, volume={31}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.14627}, DOI={10.1111/jvim.14627}, abstractNote={Respiratory tract disease can be associated with primary or secondary bacterial infections in dogs and cats and is a common reason for use and potential misuse, improper use, and overuse of antimicrobials. There is a lack of comprehensive treatment guidelines such as those that are available for human medicine. Accordingly, the International Society for Companion Animal Infectious Diseases convened a Working Group of clinical microbiologists, pharmacologists, and internists to share experiences, examine scientific data, review clinical trials, and develop these guidelines to assist veterinarians in making antimicrobial treatment choices for use in the management of bacterial respiratory diseases in dogs and cats.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Lappin, M.R. and Blondeau, J. and Boothe, D. and Breitschwerdt, E.B. and Guardabassi, L. and Lloyd, D.H. and Papich, M.G. and Rankin, S.C. and Sykes, J.E. and Turnidge, J. and et al.}, year={2017}, month={Feb}, pages={279–294} }
 @article{sypniewski_maxwell_murray_brandao_papich_2017, title={CEFOVECIN PHARMACOKINETICS IN THE RED-EARED SLIDER}, volume={26}, ISSN={["1931-6283"]}, DOI={10.1053/j.jepm.2017.01.027}, abstractNote={Abstract The administration of long‐acting antimicrobial agents to treat susceptible bacterial infections in exotic animals is desirable, as it may reduce handling stress, increase therapeutic compliance, and decrease morbidity and mortality. Cefovecin sodium, a third‐generation cephalosporin, is administered to treat susceptible bacterial infections in dogs and cats. Cefovecin has an extended dosing interval partially because of increased ability to bind with plasma protein. As such, investigations into the pharmacokinetics of this antibiotic have been conducted in zoo and exotic animal species, including terrestrial chelonians. The objective of this project was to determine the pharmacokinetic profile and protein binding of cefovecin in the red‐eared slider (Trachemys scripta elegans). Eleven healthy red‐eared sliders were administered 10 mg/kg of cefovecin subcutaneously in the forelimb. Blood samples were obtained at 2, 4, 8, 12, 24, and 48 hours postadministration. Plasma cefovecin concentrations were analyzed by reversed‐phase high‐performance liquid chromatography, and protein binding was determined using ultrafiltration. Noncompartmental pharmacokinetic analysis was performed on the resulting data. Cefovecin was rapidly absorbed, with a maximal measured plasma drug concentration of 32.3 (±23.8) &mgr;g/mL occurring at 2.4 (±1.2) hours and a terminal‐phase half‐life of 6.8 (±1.2) hours, which was much shorter than the half‐life observed in dogs and cats (approximately 5 and 7 days, respectively). No substantial side effects were noted in subjects following antibiotic administration. Although well tolerated in red‐eared sliders, the rapid decline in plasma cefovecin concentration, presumably due to the absence of plasma protein binding, negates its use as a long‐acting antibiotic in this species.}, number={2}, journal={JOURNAL OF EXOTIC PET MEDICINE}, author={Sypniewski, Lara A. and Maxwell, Lara K. and Murray, Jill K. and Brandao, Joao L. and Papich, Mark G.}, year={2017}, month={Apr}, pages={108–113} }
 @article{papich_lindeman_2017, title={Cephalexin susceptibility breakpoint for veterinary isolates: Clinical Laboratory Standards Institute revision}, volume={30}, ISSN={1040-6387 1943-4936}, url={http://dx.doi.org/10.1177/1040638717742434}, DOI={10.1177/1040638717742434}, abstractNote={ The Clinical and Laboratory Standards Institute (CLSI) uses cephalothin as the class representative for testing veterinary isolates for susceptibility to other first-generation cephalosporins, including cephalexin. We examined replacing cephalothin with cephalexin because cephalexin is used more often clinically. Bacterial isolates were obtained from dogs and cats from a national surveillance program. CLSI testing methods were used to determine the MIC for 4 cephalosporins used in veterinary medicine. Cephalexin clinical breakpoints for canine isolates were established by using published pharmacokinetic data and Monte Carlo simulations to calculate the probability of target attainment (PTA). For 1,112 Staphylococcus pseudintermedius isolates, the mode, MIC50, and MIC90 were 1, 2, and 64 µg/mL, respectively, for cephalexin, and ≤0.06, 0.12, and 2 µg/mL for cephalothin. Susceptibility of S. pseudintermedius from 2011 to 2014 did not change for the 4 cephalosporins tested. Only 4.3% of the penicillin-binding protein 2a–positive S. pseudintermedius isolates had MIC values ≤2 µg/mL for cephalexin, but 66.3% of these isolates had MIC values ≤2 µg/mL for cephalothin. There were also discrepancies between cephalexin and cephalothin for other bacteria tested, but the largest difference was for S. pseudintermedius, with a MIC difference of 4 doubling dilutions. Cephalexin interpretive categories (breakpoints) of ≤2 μg/mL (susceptible), 4 μg/mL (intermediate), and ≥8 μg/mL (resistant) were established for isolates obtained from dogs. Cephalothin should not be used for susceptibility testing of cephalexin for veterinary bacterial pathogens, and canine-specific breakpoints should be used for testing susceptibility. Breakpoints determined using the methods described herein for the interpretive categories will be added to future CLSI tables to reflect this recommendation. }, number={1}, journal={Journal of Veterinary Diagnostic Investigation}, publisher={SAGE Publications}, author={Papich, Mark G. and Lindeman, Cindy}, year={2017}, month={Nov}, pages={113–120} }
 @article{adrian_papich_baynes_murrell_lascelles_2017, title={Chronic maladaptive pain in cats: A review of current and future drug treatment options}, volume={230}, ISSN={1090-0233}, url={http://dx.doi.org/10.1016/J.TVJL.2017.08.006}, DOI={10.1016/J.TVJL.2017.08.006}, abstractNote={Despite our increasing understanding of the pathophysiology underlying chronic or maladaptive pain, there is a significant gap in our ability to diagnose and treat the condition in domestic cats. Newer techniques being used to identify abnormalities in pain processing in the cat include validated owner questionnaires, measurement of movement and activity, and measurement of sensory thresholds and somatomotor responses. While some data are available evaluating possible therapeutics for the treatment of chronic pain in the cat, most data are limited to normal cats. This review details our current understanding of chronic or maladaptive pain, techniques for the detection and measurement of the condition and the associated central nervous changes, as well as an overview of the data evaluating potential therapeutics in cats.}, journal={The Veterinary Journal}, publisher={Elsevier BV}, author={Adrian, Derek and Papich, Mark and Baynes, Ron and Murrell, Jo and Lascelles, B. Duncan X.}, year={2017}, month={Dec}, pages={52–61} }
 @article{papich_2017, title={Ciprofloxacin Pharmacokinetics in Clinical Canine Patients}, volume={31}, url={https://doi.org/10.1111/jvim.14788}, DOI={10.1111/jvim.14788}, abstractNote={BackgroundCiprofloxacin generic tablets approved for human use frequently are administered to dogs for treatment of bacterial infections because they are inexpensive and readily available. However, previous work indicated low and variable oral absorption in healthy research dogs.ObjectiveTo examine orally administered ciprofloxacin in a group of clinical canine patients using population pharmacokinetics in order to identify minimum inhibitory concentrations (MIC) that potentially could be achieved with orally administered ciprofloxacin in dogs.AnimalsThirty‐four clinical canine patients; mean weight, 22.95 kg (range, 4.6–57 kg).MethodsCiprofloxacin generic tablets intended for human use were administered to dogs in a prospective study (mean dose, 23.5 mg/kg). Sparse blood sampling was used to obtain population pharmacokinetic results with nonlinear mixed‐effects modeling. These data were used to estimate a breakpoint for susceptible bacteria. Monte Carlo simulations were used to determine the probability of target attainment (PTA) for an area under the curve (AUC)/MIC ratio of ≥100, the pharmacokinetic‐pharmacodynamic target for fluoroquinolones.ResultsThe values for volume of distribution, peak concentration, and half‐life were 10.7 L/kg (11.7%), 1.9 μg/mL (11.66%), and 4.35 hours (7.62%), respectively (mean, % coefficient of variation [CV]). The size of the dog was an important covariate with larger dogs achieving lower plasma drug concentrations than smaller dogs, despite a similar mg/kg dose. Ninety percent PTA was obtained for a MIC ≤ 0.06 μg/mL.Conclusions and Clinical ImportanceA breakpoint (susceptible) of ≤0.06 μg/mL should be considered when ciprofloxacin tablets are administered to dogs at a dose of 25 mg/kg once daily, which is much lower than the breakpoint of ≤1 μg/mL in humans.}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley-Blackwell}, author={Papich, M.G.}, year={2017}, month={Sep}, pages={1508–1513} }
 @article{foster_sylvester_papich_2017, title={Comparison of direct sampling and brochoalveolar lavage for determining active drug concentrations in the pulmonary epithelial lining fluid of calves injected with enrofloxacin or tilmicosin}, volume={40}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12412}, DOI={10.1111/jvp.12412}, abstractNote={Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril® 100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil® 300) was administered at a dose of 20 mg/kg SC. PELF, sampled by two different methods—bronchoalveolar lavage (BAL) and direct sampling (DS)—plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by AUC in DS samples was 137 ± 72% higher than in plasma, but in BAL samples, this value was 535 ± 403% (p < .05). The concentrations of tilmicosin in DS and BAL samples exceeded plasma drug concentrations by 567 ± 189% and 776 ± 1138%, respectively. The enrofloxacin/ciprofloxacin concentrations collected by DS were significantly different than those collected by BAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine respiratory disease pathogens but tilmicosin did not reach MIC levels for these pathogens in any fluids.}, number={6}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Foster, D. M. and Sylvester, H. J. and Papich, M. G.}, year={2017}, month={Apr}, pages={e45–e53} }
 @article{papich_2017, title={Considerations for using minocycline vs doxycycline for treatment of canine heartworm disease}, volume={10}, ISSN={1756-3305}, url={http://dx.doi.org/10.1186/s13071-017-2449-1}, DOI={10.1186/s13071-017-2449-1}, abstractNote={Doxycycline has been considered the first drug of choice for treating Wolbachia, a member of the Rickettsiaceae, which has a symbiotic relationship with filarial worms, including heartworms. Wolbachia, is susceptible to tetracyclines, which have been used as adjunctive treatments for heartworm disease. Treatment with doxycycline reduces Wolbachia numbers in all stages of heartworms and improves outcomes and decreased microfilaremia in dogs treated for heartworm disease. The American Heartworm Society recommends treatment with doxycycline in dogs diagnosed with heartworm disease at a dose of 10 mg/kg twice daily for 28 days. If doxycycline is not available, minocycline can be considered as a substitute. However, minocycline has not undergone an evaluation in dogs with heartworm disease, nor has an effective dose been established. Minocycline is an attractive option because of the higher cost of doxycycline and new pharmacokinetic information for dogs that provides guidance for appropriate dosage regimens to achieve pharmacokinetic-pharmacodynamic (PK-PD) targets. Published reports from the Anti-Wolbachia Consortium (A-WOL) indicate superior in vitro activity of minocycline over doxycycline. Studies performed in mouse models to measure anti-Wolbachia activity showed that minocycline was 1.7 times more effective than doxycycline, despite a 3-fold lower pharmacokinetic exposure. To achieve the same exposure as achieved in the mouse infection model, a pharmacokinetic-pharmacodynamic (PK-PD) analysis was conducted to determine optimal dosages for dogs. The analysis showed that an oral minocycline dose of 3.75 to 5 mg/kg administered twice daily would attain similar targets as observed in mice and predicted for human infections. There are potentially several advantages for use of minocycline in animals. It is well absorbed from oral administration, it has less protein binding than doxycycline (65% vs 92%) allowing for better distribution into tissue, and it is approximately two times more lipophilic than doxycycline, which may result in better intracellular penetration. More work is needed to document efficacy of minocycline for treating canine heartworm disease.}, number={S2}, journal={Parasites & Vectors}, publisher={Springer Nature}, author={Papich, Mark G.}, year={2017}, month={Nov} }
 @article{thompson_papich_higgins_flanagan_christiansen_harms_2017, title={Ketoprofen pharmacokinetics of R
- and S
-isomers in juvenile loggerhead sea turtles (Caretta caretta
) after single intravenous and single- and multidose intramuscular administration}, volume={41}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12460}, DOI={10.1111/jvp.12460}, abstractNote={Ketoprofen is a nonsteroidal anti‐inflammatory and analgesic agent that nonselectively inhibits cyclooxygenase, with both COX‐1 and COX‐2 inhibition. Recent studies on COX receptor expression in reptiles suggest that nonselective COX inhibitors may be more appropriate than more selective inhibitors in some reptiles, but few pharmacokinetic studies are available. The goal of this study was to determine single‐ and multidose (three consecutive days) pharmacokinetics of racemic ketoprofen administered intravenously and intramuscularly at 2 mg/kg in healthy juvenile loggerhead turtles (Caretta caretta). The S‐isomer is the predominant isomer in loggerhead sea turtles, similar to most mammals, despite administration of a 50:50 racemic mixture. Multidose ketoprofen administration demonstrated no bioaccumulation; therefore, once‐daily dosing will not require dose adjustment over time. S‐isomer pharmacokinetic parameters determined in this study were Cmax of 10.1 μg/ml by IM injection, C0 of 13.4 μg/ml by IV injection, AUC of 44.7 or 69.4 μg*hr/ml by IM or IV injection, respectively, and T½ of 2.8 or 3.6 hr by IM or IV injection, respectively. Total ketoprofen plasma concentrations were maintained for at least 12 hr above concentrations determined to be effective for rats and humans. A dose of 2 mg/kg either IM or IV every 24 hr is likely appropriate for loggerhead turtles.}, number={2}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Thompson, K. A. and Papich, M. G. and Higgins, B. and Flanagan, J. and Christiansen, E. F. and Harms, C. A.}, year={2017}, month={Oct}, pages={340–348} }
 @article{sweeney_papich_watts_2017, title={New interpretive criteria for danofloxacin antibacterial susceptibility testing against Mannheimia haemolytica and Pasteurella multocida associated with bovine respiratory disease}, volume={29}, ISSN={["1943-4936"]}, DOI={10.1177/1040638716683212}, abstractNote={ Danofloxacin is a fluoroquinolone antibacterial agent approved for use in veterinary medicine to treat and control bovine respiratory disease caused by Mannheimia haemolytica or Pasteurella multocida. Susceptible minimal inhibitory concentration (MIC) breakpoint (≤0.25 µg/mL) and disk diffusion interpretive criteria (≥22 mm) values for danofloxacin against M. haemolytica and P. multocida were first approved by the Clinical and Laboratory Standards Institute (CLSI) in 2003. However, intermediate and resistant breakpoint values were not established because only susceptible wild-type populations were evident at the time of breakpoint approvals. Since then, nonsusceptible isolates of M. haemolytica and P. multocida have been identified. We report danofloxacin intermediate MIC breakpoint (0.5 µg/mL) and disk diffusion interpretive criteria (18–21 mm), as well as danofloxacin-resistant MIC breakpoint (≥1 µg/mL) and disk diffusion interpretive criteria (≤17 mm), based on scattergram plots of MIC values versus disk zone diameters and calculated error-bound rates using M. haemolytica and P. multocida isolates recovered from bovine respiratory disease in North America in 2004–2014. These newly established intermediate and resistant clinical breakpoint values have been endorsed by CLSI and can be used for interpreting results from antibacterial susceptibility testing of danofloxacin against M. haemolytica and P. multocida isolated from bovine respiratory disease. }, number={2}, journal={JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION}, author={Sweeney, Michael T. and Papich, Mark G. and Watts, Jeffrey L.}, year={2017}, month={Mar}, pages={224–227} }
 @article{hasbach_langlois_rosser_papich_2017, title={Pharmacokinetics and Relative Bioavailability of Orally Administered Innovator-Formulated Itraconazole Capsules and Solution in Healthy Dogs}, volume={31}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.14779}, DOI={10.1111/jvim.14779}, abstractNote={BackgroundItraconazole is commonly used for treatment of systemic and cutaneous mycoses in veterinary medicine. Two formulations, capsule and solution, are used interchangeably in dogs. However, marked differences in bioavailability have been reported in other species. Similar investigations have not been performed in dogs.ObjectiveTo determine and compare pharmacokinetics of itraconazole in dogs after oral administration of commercially available capsule and solution formulations intended for use in humans.AnimalsEight healthy, adult, purpose‐bred dogs.MethodsDogs received approximately 10 mg/kg of innovator‐formulated itraconazole solution and capsule PO in randomized, crossover design with a 10‐day washout period. To ensure maximal absorption, solution was administered to fasted dogs, whereas capsules were co‐administered with food. Blood samples were collected at predetermined time points, and plasma drug concentrations were measured using high‐pressure liquid chromatography. Pharmacokinetic parameters were determined with compartmental analysis.ResultsThe mean relative bioavailability of the capsule was 85% that of the solution, but drug absorption was variable, and overall drug concentrations were similar between formulations. Mean elimination half‐lives of both formulations were nearly identical at approximately 33 hours. Regardless of formulation, simulations suggest that a loading dose of 20 mg/kg, followed by 10 mg/kg once every 24 hours, will result in plasma concentrations considered to be adequate in most dogs.Conclusions and Clinical ImportanceContrary to findings reported in other species, overall drug exposures after capsule and solution administration are not substantially different in dogs. Despite some pharmacokinetic differences between itraconazole capsule and solution, formulation‐specific dosages do not appear to be necessary.}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, publisher={Wiley-Blackwell}, author={Hasbach, A. E. and Langlois, D. K. and Rosser, E. J., Jr. and Papich, M. G.}, year={2017}, pages={1163–1169} }
 @article{depenbrock_simpson_niehaus_lakritz_papich_2017, title={Pharmacokinetics of ampicillin-sulbactam in serum and synovial fluid samples following regional intravenous perfusion in the distal portion of a hind limb of adult cattle}, volume={78}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.78.12.1372}, abstractNote={Abstract
OBJECTIVE To describe concentration-over-time data for ampicillin and sulbactam in the digital and systemic circulations and synovial fluid (SYN) of cattle following a single injection of ampicillin-sulbactam as a regional IV perfusion (RIVP).
ANIMALS 6 healthy adult nonlactating Jersey-crossbred cows.
PROCEDURES The right hind limb of each cow was aseptically prepared. A tourniquet was applied around the midmetatarsal region, and 1.0 g of ampicillin with 0.5 g of sulbactam in a combined formulation was administered as an RIVP into the dorsal common digital vein (DCDV). Blood samples from the DCDV and jugular vein and SYN samples from the metatarsophalangeal joint of the prepared limb were collected immediately before and at predetermined times for 24 hours after RIVP. One blood sample was obtained from the abaxial proper plantar vein of the lateral digit of the prepared limb 0.25 hours after RIVP. Serum and SYN ampicillin and sulbactam concentrations were determined by high-performance liquid chromatography.
RESULTS Mean ± SD maximum concentration of ampicillin in SYN and serum obtained from the abaxial proper plantar and jugular veins was 1,995 ± 1,011 μg/mL, 5,422 ± 1,953 μg/mL, and 2.5 ± 1.6 μg/mL, respectively. Corresponding serum and SYN concentrations of sulbactam were lower but followed the same pattern over time as those for ampicillin. Synovial fluid ampicillin concentration remained above 8 μg/mL for a mean time of 18.9 hours.
CONCLUSIONS AND CLINICAL RELEVANCE Potentially therapeutic concentrations of ampicillin were achieved in regional serum and SYN samples; SYN concentrations remained at potentially therapeutic values for > 12 hours following RIVP of 1.5 g of ampicillin-sulbactam in the hind limb of healthy cows.}, number={12}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Depenbrock, Sarah M. and Simpson, Katharine M. and Niehaus, Andrew J. and Lakritz, Jeffrey and Papich, Mark G.}, year={2017}, month={Dec}, pages={1372–1379} }
 @article{kirby_lewbart_hancock-ronemus_papich_2018, title={Pharmacokinetics of enrofloxacin and ciprofloxacin in Atlantic horseshoe crabs (Limulus polyphemus) after single injection}, volume={41}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/jvp.12462}, DOI={10.1111/jvp.12462}, abstractNote={The pharmacokinetics of enrofloxacin and the metabolite ciprofloxacin were studied in horseshoe crabs after a single injection of 5 mg/kg. Twelve Atlantic horseshoe crabs (Limulus polyphemus) of undetermined age were injected with enrofloxacin into the dorsal cardiac sinus. Hemolymph samples were collected by syringe and needle at regular intervals for 120 hr. Samples were analyzed by high‐pressure liquid chromatography and compartmental analysis performed on the results. Following injection, the elimination half‐life (T½), peak concentration, area under the curve (AUC), and volume of distribution (VD) for enrofloxacin were 27.9 (29.13) hr, 8.98 (18.09) μg/ml, 367.38 (35.41) hr μg/ml, and 0.575 (20.48) L/kg, respectively (mean value, CV%). For ciprofloxacin, the elimination T½, peak concentration, and AUC were 61.36 (34.55) hr, 2.34 (24.11) μg/ml, and 304.46 (24.69) μg hr/ml. In these animals, the ciprofloxacin concentrations comprised an average of 45.8% of the total fluoroquinolone concentrations, which is substantial compared to other marine invertebrates. The total AUC produced (sum of enrofloxacin and ciprofloxacin) was 682.69 ± 180.61 μg hr/ml. Concentrations that were achieved after a single dose of 5 mg/kg horseshoe crabs were sufficient to treat bacteria susceptible to enrofloxacin and ciprofloxacin.}, number={2}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, publisher={Wiley-Blackwell}, author={Kirby, A. and Lewbart, G. A. and Hancock-Ronemus, A. and Papich, M. G.}, year={2018}, month={Apr}, pages={349–353} }
 @article{watson_papich_chinnadurai_2017, title={Pharmacokinetics of intravenous clindamycin phosphate in captive Bennett's wallabies (Macropus rufogriseus)}, volume={40}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12421}, abstractNote={This study was designed to investigate the pharmacokinetics of clindamycin, a lincosamide antibiotic, in Bennett's wallabies. The pharmacokinetic properties of a single intravenous (IV) dose of clindamycin were determined in six wallabies. A single 20‐min IV infusion of 20 mg/kg of clindamycin was administered, followed by blood collection prior to, and up to 12 hr after clindamycin administration. Plasma clindamycin concentrations were determined by high‐pressure liquid chromatography (HPLC) with ultraviolet (UV) detection. Pharmacokinetic variables were calculated using a two‐compartment model with first order elimination which best fit the data. The mean volume of distribution at steady‐state, distribution half‐life, and elimination half‐life were 898.25 ml/kg, 0.16 hr, 1.79 hr, respectively. No adverse effects were noted after IV administration.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Watson, M. K. and Papich, M. G. and Chinnadurai, S. K.}, year={2017}, month={Dec}, pages={682–686} }
 @inbook{papich_2017, place={St. Louis, Missouri}, edition={Eighth}, title={Section Advisor: Therapeutic Considerations in Medicine and Disease}, booktitle={Textbook of Veterinary Internal Medicine: Disease of the Dog and the Cat}, publisher={Elsevier}, author={Papich, M.G.}, editor={Ettinger, S.J. and Feldman, E.C. and Côté, E.Editors}, year={2017} }
 @article{papich_2016, title={Antimicrobial susceptibility testing for feline urinary tract isolates}, volume={18}, ISSN={1098-612X 1532-2750}, url={http://dx.doi.org/10.1177/1098612x15620450}, DOI={10.1177/1098612x15620450}, abstractNote={I am writing on behalf of the Veterinary Antimicrobial Susceptibility Testing (VAST) subcommittee of the Clinical and Laboratory Standards Institute (CLSI) with regard to the paper by Lund et al,1 ‘Antimicrobial susceptibility in bacterial isolates from Norwegian cats with lower urinary tract disease’, published in the June 2015 issue of the Journal of Feline Medicine and Surgery (JFMS). The authors are commended for providing new information on the bacterial isolates from cats with lower urinary tract disease. New data on bacteria cultured from cats can be helpful for clinicians and scientists who wish to improve treatment of lower urinary tract disease. However, we have some questions and some points with regard to the susceptibility testing presented in the paper. The authors indicated in the Materials and methods section that ‘Susceptibility to antimicrobial agents was determined in accordance with the recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST)’. They indicated that susceptibility of isolates from cats was determined for ‘penicillin, ampicillin, amoxicillin with and without clavulanic acid, cephalexin, trimethoprim, trimethoprim/sulfonamide, tetracycline, fucidic [sic] acid, enrofloxacin, spiramycin, lincomycin and nitrofurantoin’. However, the EUCAST recommendations do not have any clinical breakpoints for isolates from cats. EUCAST only provides breakpoints for isolates from humans. Differences in pathogens, antimicrobial doses, and especially differences in pharmacokinetics and pharmacokinetic–pharmacodynamic relationships between cats and humans make the use of human breakpoints to predict susceptibility for cat isolates potentially unreliable. In the Discussion of the paper, the authors compared their results with those of other published studies. Unless each study uses the same standards for testing, such comparisons can lead to incorrect conclusions. An examination of the EUCAST breakpoints indicates that clinical breakpoints are not listed for many of the drugs listed in the authors’ results. For example, some drugs are not used in humans (eg, enrofloxacin) and no human breakpoint exists. The authors tested susceptibility of Enterococcus and Pasteurella species to 13 antimicrobials, yet there are only a few antimicrobials for which EUCAST has a human breakpoint listed for these bacteria. The CLSI standard for testing Enterococcus species (M100)2 indicates that cephalosporins, clindamycin and trimethoprim-sulfamethoxazole may appear active in vitro, but they are not effective clinically, and isolates should not be reported as susceptible. Most of the drugs listed in the susceptibility results for Enterococcus species isolates in the paper are not recommended for testing by the CLSI. It is possible that the authors of this paper may have used the wild-type cutoff (also known as the epidemiological cutoff or ECOFF) to indicate susceptibility of these bacteria to the antimicrobials listed in their paper. The ECOFF and the breakpoint (also called the clinical breakpoint) are not the same.3 They are determined using different criteria and the values are often quite dissimilar for many antimicrobials. An isolate with an MIC value above the ECOFF is not necessarily defined as ‘resistant’ using the breakpoint and interpretive criteria. The VAST is a subcommittee of the CLSI. This is the only global organization that provides public standards for antimicrobial susceptibility testing for bacteria isolated from animals.4,5 The CLSI procedure for establishing susceptibility testing breakpoints is a consensus-driven process. Breakpoints for animals are determined after analyzing pharmacokinetic and pharmacodynamic data, MIC distributions, and considering clinical data. An examination of Table 2 from the CLSI– VAST document shows many differences between the human breakpoint and the veterinary-specific breakpoint for the same antimicrobial agent. The human breakpoint is often not accurate for animals and we encourage laboratories to use the criteria determined by the CLSI whenever possible. We appreciate the opportunity to clarify some of the points addressed in the paper by Lund et al.1 We invite authors of manuscripts submitted to JFMS to consult with our CLSI–VAST subcommittee when there are questions regarding susceptibility testing of bacterial isolates from Antimicrobial susceptibility testing for feline urinary tract isolates 620450 JFM0010.1177/1098612X15620450Journal of Feline Medicine and SurgeryLetter to the Editor letter2015}, number={2}, journal={Journal of Feline Medicine and Surgery}, publisher={SAGE Publications}, author={Papich, Mark G}, year={2016}, month={Jan}, pages={183–184} }
 @article{risselada_marcellin-little_messenger_griffith_davidson_papich_2016, title={Assessment of in vitro release of carboplatin from six carrier media}, volume={77}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.77.12.1381}, abstractNote={Abstract
OBJECTIVE To investigate in vitro carboplatin release from 6 carrier media.
SAMPLE 6 carboplatin-containing carrier media.
PROCEDURES An in vitro release study was performed with 6 commercially available carrier media: a hemostatic gelatin sponge, a poloxamer copolymer gel, and 2 sizes (3 and 4.8 mm in diameter) of beads molded from each of 2 commercial calcium sulfate products. All carrier media contained 10 mg of carboplatin. Carrier media specimens were placed in 37°C PBS solution for 96 hours. Carboplatin concentrations in PBS solution were measured by use of high-performance liquid chromatography at 15 time points to calculate the amount and proportion of carboplatin released from each specimen.
RESULTS Peak release of carboplatin from the poloxamer copolymer gel and hemostatic gelatin sponge were achieved after 4 and 20 hours, respectively. Maximum release did not differ significantly between the poloxamer copolymer gel and hemostatic gelatin sponge, but both released significantly more carboplatin within 96 hours than did both of the commercial calcium sulfate products. The poloxamer copolymer gel released 99% of the carboplatin, and the hemostatic gelatin sponge released 68.5% of the carboplatin. Peak release of carboplatin from the calcium sulfate beads was not reached within 96 hours.
CONCLUSIONS AND CLINICAL RELEVANCE In this study, carboplatin release from the hemostatic gelatin sponge was incomplete. The poloxamer copolymer gel and hemostatic gelatin sponge released carboplatin rapidly in vitro, whereas calcium sulfate beads did not.}, number={12}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Risselada, Marije and Marcellin-Little, Denis J. and Messenger, Kristen M. and Griffith, Emily and Davidson, Gigi S. and Papich, Mark G.}, year={2016}, month={Dec}, pages={1381–1386} }
 @article{foster_martin_papich_2016, title={Comparison of active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of calves injected with enrofloxacin, florfenicol, ceftiofur, or tulathromycin}, volume={11}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0149100}, DOI={10.1371/journal.pone.0149100}, abstractNote={Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900% penetration to the airways. Despite high diffusion into the bronchi, the tulathromycin concentrations achieved were lower than the MIC of susceptible bacteria at most time points.}, number={2}, journal={PLoS One}, publisher={PMC}, author={Foster, Derek M. and Martin, Luke G. and Papich, Mark G.}, editor={Torrelles, Jordi B.Editor}, year={2016}, month={Feb}, pages={e0149100} }
 @article{foster_martin_papich_2016, title={Correction: Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin}, volume={11}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0159219}, DOI={10.1371/journal.pone.0159219}, abstractNote={[This corrects the article DOI: 10.1371/journal.pone.0149100.].}, number={7}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Foster, Derek M. and Martin, Luke G. and Papich, Mark G.}, year={2016}, month={Jul}, pages={e0159219} }
 @inbook{papich_2016, edition={6th}, title={Drug Formulary, Appendix IX}, booktitle={Blackwells's Five Minute Veterinary Consult: Canine and Feline}, publisher={Wiley Blackwell}, author={Papich, M.G.}, editor={Tilley, L.P. and Smith, F.W.K.Editors}, year={2016}, pages={1445–1548} }
 @article{adin_atkins_papich_defrancesco_griffiths_penteado_kurtz_klein_2017, title={Furosemide continuous rate infusion diluted with 5% dextrose in water or hypertonic saline in normal adult dogs: a pilot study}, volume={19}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2016.09.004}, abstractNote={{"Label"=>"OBJECTIVE", "NlmCategory"=>"OBJECTIVE"} The goal of this study was to investigate the short-term safety and diuretic efficacy of furosemide constant rate infusion (CRI) diluted with 5% dextrose in water (D5W) compared to dilution with 2.4% hypertonic saline in healthy dogs. {"Label"=>"ANIMALS", "NlmCategory"=>"METHODS"} Six healthy dogs. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} Dogs were studied in a randomized, blinded, crossover manner. Furosemide 3.3mg/kg was diluted to 2.2mg/mL with either 1.5mL/kg D5W for the DEX method or with 1.0mL/kg D5W and 0.5mL/kg of 7.2% hypertonic saline for the H-SAL method. After a 0.66mg/kg furosemide IV bolus, the infusion rate was 0.3 mL/kg/hr for 5 h such that both methods delivered 0.66 mg/kg/hr (total 3.3mg/kg) furosemide in equal volume for the study duration. Urine output, water intake, central venous pressure (CVP), physical parameters, furosemide concentrations, blood and urine electrolytes, and urine aldosterone to creatinine ratio (UAldo:C) were evaluated. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} Measured variables were not different between methods but showed changes over time consistent with diuresis. Mean CVP decreased over time similarly for both methods. Plasma furosemide and urine concentrations were stable and not different between methods. Both furosemide CRI methods showed an increase in the UAldo:C, however, the rise was greater for DEX than for H-SAL. {"Label"=>"CONCLUSIONS", "NlmCategory"=>"CONCLUSIONS"} Diuresis was similar for both furosemide CRI methods; however, the H-SAL method induced less renin-angiotensin-aldosterone system activation than the DEX method. The absence of intravascular volume expansion based on CVP suggests that dilution of a furosemide CRI with 2.4% hypertonic saline may be well tolerated in heart failure.}, number={1}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Adin, D. and Atkins, C. and Papich, M. and DeFrancesco, T. and Griffiths, E. and Penteado, M. and Kurtz, K. and Klein, A.}, year={2017}, month={Feb}, pages={44–56} }
 @article{papich_brown_kirk_2016, title={How to (properly) determine the beyond-use date and stability of a compounded formulation for pets}, volume={18}, number={4}, journal={Journal of Feline Medicine & Surgery}, author={Papich, M.G. and Brown, S. and Kirk, L.}, year={2016}, pages={364–365} }
 @article{phillips_harms_lewbart_lahner_haulena_rosenberg_papich_2016, title={POPULATION PHARMACOKINETICS OF ENROFLOXACIN AND ITS METABOLITE CIPROFLOXACIN IN THE GREEN SEA URCHIN (STRONGYLOCENTROTUS DROEBACHIENSIS) FOLLOWING INTRACOELOMIC AND IMMERSION ADMINISTRATION}, volume={47}, ISSN={1042-7260 1937-2825}, url={http://dx.doi.org/10.1638/2015-0110.1}, DOI={10.1638/2015-0110.1}, abstractNote={Abstract Sea urchin mass mortality events have been attributed to both infectious and noninfectious etiologies. Bacteria, including Vibrio spp. and Pseudoalteromonas spp., have been isolated during specific mortality events. Aquarium collection sea urchins are also subject to bacterial infections and could benefit from antimicrobial treatment, but pharmacokinetic studies have been lacking for this invertebrate group until recently. This study evaluated the pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin in the green sea urchin (Strongylocentrotus droebachiensis) after intracoelomic injection and medicated bath immersion administration. The utility of a population pharmacokinetic method using nonlinear mixed effects modeling (NLME) was also evaluated. Thirty sea urchins were assigned to either the injection or immersion group. Twelve study animals and three untreated controls were utilized for each administration method: enrofloxacin 10 mg/kg intracoelomic injection or a 6-hr enrofloxacin 10 mg/L immersion. Each animal was sampled four times from 0 to 120 hr. Water samples were collected during immersion treatment and posttreatment time points in both groups. Hemolymph and water sample drug concentrations were analyzed using high-performance liquid chromatography, and pharmacokinetic parameters were determined using an NLME population pharmacokinetic method. Enrofloxacin concentrations were fit to a two-compartment model with first-order input for the intracoelomic injection group. The enrofloxacin elimination half-life (t½), peak hemolymph concentration (CMAX), and area under the curve (AUC) were 38.82 hr, 90.92 μg/ml, and 1,199 hr·μg/ml, respectively. Enrofloxacin was modeled to a one-compartment model with first-order input for the immersion treatment. The enrofloxacin t½, CMAX, and AUC were 33.46 hr, 0.48 μg/ml, and 32.88 hr·μg/ml, respectively. Ciprofloxacin was detected in trace concentrations in all hemolymph samples, indicating minimal production of this metabolite. The concentrations of enrofloxacin achieved far exceeded minimum inhibitory concentrations reported for teleost pathogens. No adverse effects were associated with enrofloxacin administration by either treatment method or from hemolymph sampling.}, number={1}, journal={Journal of Zoo and Wildlife Medicine}, publisher={American Association of Zoo Veterinarians}, author={Phillips, Brianne E. and Harms, Craig A. and Lewbart, Gregory A. and Lahner, Lesanna L. and Haulena, Martin and Rosenberg, Justin F. and Papich, Mark G.}, year={2016}, month={Mar}, pages={175–186} }
 @article{pollock_bedenice_jennings_papich_2017, title={Pharmacokinetics of an extended-release formulation of eprinomectin in healthy adult alpacas and its use in alpacas confirmed with mange}, volume={40}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12341}, abstractNote={The study objective was to determine the pharmacokinetics and clinical effects of an extended‐release 5% eprinomectin formulation (Longrange®) following subcutaneous (s.c.) injection in healthy (n = 6) and mange‐infected (n = 4) adult alpacas. High‐performance liquid chromatography was used to analyze plasma samples obtained at regular intervals for 161 days following a single 5 mg/kg injection s.c. in healthy alpacas, and for 5 days following each dose (3 treatments, 2 months apart) in mange‐affected animals. Skin scrapings and biopsies were performed pre‐ and post‐treatment at two comparable sites in alpacas with mange. Four alpacas served as healthy controls. Eprinomectin plasma concentrations showed a biphasic peak (CMAX‐1: 5.72 ± 3.25 ng/mL; CMAX‐2: 6.06 ± 2.47 ng/mL) in all animals at 3.88 ± 5.16 days and 77 ± 12.52 days, respectively. Eprinomectin plasma concentrations remained above 1.27 ± 0.96 ng/mL for up to 120 days. Hematocrit (35.8 vs. 31.3%, P < 0.003) and albumin (3.5 vs. 2.8 g/dL P < 0.006) reduced significantly over 6 months in multidose animals, while fecal egg counts did not differ between groups. Self‐limiting injection site reactions occurred in 9 of 10 animals. Pre‐ and post‐treatment skin biopsies showed reduced hyperkeratosis, but increased fibrosis, with 1 of 4 alpacas remaining positive on skin scraping for mange. In conclusion, alpacas require a higher eprinomectin dose (5.0 mg/kg s.c.) than cattle, to reach comparable plasma concentrations.}, number={2}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Pollock, J. and Bedenice, D. and Jennings, S. H. and Papich, M. G.}, year={2017}, month={Apr}, pages={192–199} }
 @article{messenger_hopfensperger_knych_papich_2016, title={Pharmacokinetics of detomidine following intravenous or oral-transmucosal administration and sedative effects of the oral-transmucosal treatment in dogs}, volume={77}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.77.4.413}, abstractNote={Abstract
OBJECTIVE To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs.
ANIMALS 12 healthy adult dogs.
PROCEDURES In phase 1, detomidine was administered by IV (0.5 mg/m2) or OTM (1 mg/m2) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m2) or detomidine gel by OTM administration (0.5 mg/m2), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment.
RESULTS Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation.
CONCLUSIONS AND CLINICAL RELEVANCE Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.}, number={4}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Messenger, Kristen M. and Hopfensperger, Marie and Knych, Heather K. and Papich, Mark G.}, year={2016}, month={Apr}, pages={413–420} }
 @article{vishkautsan_papich_thompson_sykes_2016, title={Pharmacokinetics of voriconazole after intravenous and oral administration to healthy cats}, volume={77}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.77.9.931}, abstractNote={Abstract
OBJECTIVE To determine pharmacokinetics and adverse effects after voriconazole administration to cats and identify an oral dose of voriconazole for cats that maintains plasma drug concentrations within a safe and effective range.
ANIMALS 6 healthy cats.
PROCEDURES Voriconazole (1 mg/kg, IV) was administered to each cat (phase 1). Serial plasma voriconazole concentrations were measured for 24 hours after administration. Voriconazole suspension or tablets were administered orally at 4, 5, or 6 mg/kg (phase 2). Plasma voriconazole concentrations were measured for 24 hours after administration. Pharmacokinetics of tablet and suspension preparations was compared. Finally, an induction dose of 25 mg/cat (4.1 to 5.4 mg/kg, tablet formulation), PO, was administered followed by 12.5 mg/cat (2.05 to 2.7 mg/kg), PO, every 48 hours for 14 days (phase 3). Plasma voriconazole concentration was measured on days 2, 4, 8, and 15.
RESULTS Voriconazole half-life after IV administration was approximately 12 hours. Maximal plasma concentration was reached within 60 minutes after oral administration. A dose of 4 mg/kg resulted in plasma concentrations within the target range (1 to 4 μg/mL). Adverse effects included hypersalivation and miosis. During long-term administration, plasma concentrations remained in the target range but increased, which suggested drug accumulation.
CONCLUSIONS AND CLINICAL RELEVANCE Voriconazole had excellent oral bioavailability and a long half-life in cats. Oral administration of a dose of 12.5 mg/cat every 72 hours should be investigated. Miosis occurred when plasma concentrations reached the high end of the target range. Therefore, therapeutic drug monitoring should be considered to minimize adverse effects.}, number={9}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Vishkautsan, Polina and Papich, Mark G. and Thompson, George R., III and Sykes, Jane E.}, year={2016}, month={Sep}, pages={931–939} }
 @article{early_crook_williams_davis_munana_papich_messenger_2017, title={Plasma and serum concentrations of cytarabine administered via continuous intravenous infusion to dogs with meningoencephalomyelitis of unknown etiology}, volume={40}, ISSN={["1365-2885"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84988369300&partnerID=MN8TOARS}, DOI={10.1111/jvp.12360}, abstractNote={The objective of this study was to evaluate the plasma and serum concentrations of cytarabine (CA) administered via constant rate infusion (CRI) in dogs with meningoencephalomyelitis of unknown etiology (MUE). Nineteen client‐owned dogs received a CRI of CA at a dose of 25 mg/m2/h for 8 h as treatment for MUE. Dogs were divided into four groups, those receiving CA alone and those receiving CA in conjunction with other drugs. Blood samples were collected at 0, 1, 8, and 12 h after initiating the CRI. Plasma (n = 13) and serum (n = 11) cytarabine concentrations were measured by high‐pressure liquid chromatography. The mean peak concentration (CMAX) and area under the curve (AUC) after CRI administration were 1.70 ± 0.66 μg/mL and 11.39 ± 3.37 h·μg/mL, respectively, for dogs receiving cytarabine alone, 2.36 ± 0.35 μg/mL and 16.91 + 3.60 h·μg/mL for dogs administered cytarabine and concurrently on other drugs. Mean concentrations for all dogs were above 1.0 μg/mL at both the 1‐ and 8‐h time points. The steady‐state achieved with cytarabine CRI produces a consistent and prolonged exposure in plasma and serum, which is likely to produce equilibrium between blood and the central nervous system in dogs with a clinical diagnosis of MUE. Other medications commonly used to treat MUE do not appear to alter CA concentrations in serum and plasma.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Early, P. J. and Crook, K. I. and Williams, L. M. and Davis, E. G. and Munana, K. R. and Papich, M. G. and Messenger, K. M.}, year={2017}, month={Aug}, pages={411–414} }
 @article{zordan_papich_pich_unger_sanchez_2016, title={Population pharmacokinetics of a single dose of meloxicam after oral and intramuscular administration to captive lesser flamingos (Phoeniconaias minor)}, volume={77}, DOI={10.2460/ajvr.77.12.1311}, abstractNote={Abstract
OBJECTIVE To determine the pharmacokinetics of a single dose of meloxicam after IM and oral administration to healthy lesser flamingos (Phoeniconaias minor) by use of a population approach.
ANIMALS 16 healthy captive lesser flamingos between 1 and 4 years of age.
PROCEDURES A single dose of meloxicam (0.5 mg/kg) was administered IM to each bird, and blood samples were collected from birds at 3 (n = 13 birds), 2 (2), or 1 (1) selected point between 0 and 13 hours after administration, with samples collected from birds at each point. After a 15-day washout period, the same dose of meloxicam was administered PO via a red rubber tube and blood samples were collected as described for IM administration. Pharmacokinetic values were determined from plasma concentrations measured by high-performance liquid chromatography.
RESULTS Plasma drug concentrations after IM administration of meloxicam reached a mean ± SD maximum value of 6.01 ± 3.38 μg/mL. Mean area under the concentration-versus-time curve was 17.78 ± 2.79 μg•h/mL, and mean elimination half-life was 1.93 ± 0.32 hours. Plasma concentrations after oral administration reached a mean maximum value of 1.79 ± 0.33 μg/mL. Mean area under the curve was 22.16 ± 7.17 μg•h/mL, and mean elimination half-life was 6.05 ± 3.53 hours.
CONCLUSIONS AND CLINICAL RELEVANCE In lesser flamingos, oral administration of meloxicam resulted in higher bioavailability and a longer elimination half-life than did IM administration, but the maximum plasma concentration was low and may be insufficient to provide analgesia in flamingos. Conversely, IM administration achieved the desired plasma concentration but would require more frequent administration.}, number={12}, journal={American Journal of Veterinary Research}, author={Zordan, M. A. and Papich, Mark and Pich, A. A. and Unger, K. M. and Sanchez, C. R.}, year={2016}, pages={1311–1317} }
 @article{rosenberg_haulena_phillips_harms_lewbart_lahner_papich_2016, title={Population pharmacokinetics of enrofloxacin in purple sea stars (Pisaster ochraceus) following an intracoelomic injection or extended immersion}, volume={77}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.77.11.1266}, abstractNote={Abstract
OBJECTIVE To determine population pharmacokinetics of enrofloxacin in purple sea stars (Pisaster ochraceus) administered an intracoelomic injection of enrofloxacin (5 mg/kg) or immersed in an enrofloxacin solution (5 mg/L) for 6 hours.
ANIMALS 28 sea stars of undetermined age and sex.
PROCEDURES The study had 2 phases. Twelve sea stars received an intracoelomic injection of enrofloxacin (5 mg/kg) or were immersed in an enrofloxacin solution (5 mg/L) for 6 hours during the injection and immersion phases, respectively. Two untreated sea stars were housed with the treated animals following enrofloxacin administration during both phases. Water vascular system fluid samples were collected from 4 sea stars and all controls at predetermined times during and after enrofloxacin administration. The enrofloxacin concentration in those samples was determined by high-performance liquid chromatography. For each phase, noncompartmental analysis of naïve averaged pooled samples was used to obtain initial parameter estimates; then, population pharmacokinetic analysis was performed that accounted for the sparse sampling technique used.
RESULTS Injection phase data were best fit with a 2-compartment model; elimination half-life, peak concentration, area under the curve, and volume of distribution were 42.8 hours, 18.9 μg/mL, 353.8 μg•h/mL, and 0.25 L/kg, respectively. Immersion phase data were best fit with a 1-compartment model; elimination half-life, peak concentration, and area under the curve were 56 hours, 36.3 μg•h/mL, and 0.39 μg/mL, respectively.
CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that the described enrofloxacin administration resulted in water vascular system fluid drug concentrations expected to exceed the minimum inhibitory concentration for many bacterial pathogens.}, number={11}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Rosenberg, Justin F. and Haulena, Martin and Phillips, Brianne E. and Harms, Craig A. and Lewbart, Gregory A. and Lahner, Lesanna L. and Papich, Mark G.}, year={2016}, month={Nov}, pages={1266–1275} }
 @article{mawby_whittemore_fowler_papich_2016, title={Posaconazole Pharmacokinetics in Healthy Cats after Oral and Intravenous Administration}, volume={30}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.14523}, abstractNote={BackgroundPosaconazole is the most active available azole antifungal drug, but absorption and pharmacokinetics are not available to guide dosing regimens in cats.ObjectiveTo determine the pharmacokinetics of posaconazole in cats given an IV solution and PO suspension.AnimalsSix healthy, adult research cats.MethodsAfter a 12‐hour fast, each cat received 15 mg/kg of posaconazole PO suspension with food. Four cats also received 3 mg/kg IV posaconazole after a 7‐day washout period. Plasma was collected at predetermined intervals for analysis using high‐pressure liquid chromatography (HPLC). Concentration data were analyzed using a 2‐compartment pharmacokinetic analysis for IV administration data and a 1‐compartment analysis with first‐order input for PO administration data using Phoenix® software.ResultsAfter IV dosing, volume of distribution (VSS) was 1.9 (0.3) L/kg (mean, standard deviation), terminal half‐life (T½) was 57.7 (28.4) hours, and clearance was 28.1 (17.3) mL/kg/h. After PO dosing, peak concentration (CMAX) was 1.2 (0.5) μg/mL and T½ was 38.1 (15.0) hours. Bioavailability of PO suspension was 15.9% (8.6). No adverse effects were observed with either route of administration.Conclusion and Clinical ImportanceDespite low PO absorption, these data allow for simulation of PO dosage regimens that could be explored in clinical studies. Two regimens can be considered to maintain targeted trough concentrations of 0.5–0.7 μg/mL as extrapolated from studies in humans: (1) 30 mg/kg PO loading dose followed by 15 mg/kg q48h, or (2) 15 mg/kg PO loading dose followed by 7.5 mg/kg q24h.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Mawby, D. I. and Whittemore, J. C. and Fowler, L. E. and Papich, M. G.}, year={2016}, pages={1703–1707} }
 @book{papich_2016, place={St. Louis, Missouri}, edition={Fourth}, title={Saunders Handbook of Veterinary Drugs}, publisher={Elsevier-Saunders}, author={Papich, M.G.}, year={2016} }
 @article{thames_lovvorn_papich_wills_archer_mackin_thomason_2017, title={The effects of clopidogrel and omeprazole on platelet function in normal dogs}, volume={40}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12340}, abstractNote={Omeprazole is used concurrently with clopidogrel to reduce gastrointestinal adverse effects. In humans, the concurrent use of these two drugs can reduce the antiplatelet efficacy of clopidogrel. Our objective was to determine the effects of omeprazole and clopidogrel on platelet function in healthy dogs. A crossover study utilized turbidimetric aggregometry (ADP and collagen) and the PFA‐100® with the collagen/ADP cartridge to evaluate platelet function in eight healthy dogs during the administration of clopidogrel (1 mg/kg/24 h p.o.), omeprazole (1 mg/kg/24 h p.o.), and a combination of clopidogrel and omeprazole. Drug metabolite concentrations were also measured. Compared to pretreatment, on Days 3 and 5, with ADP as the agonist, there was a significant decrease in maximum amplitude on aggregometry for both clopidogrel and clopidogrel/omeprazole groups. The following revealed no significant differences between clopidogrel and clopidogrel/omeprazole groups when compared on Days 3 and 5: maximum amplitude on aggregometry with ADP or collagen agonists, and PFA‐100® closure times. When compared to the clopidogrel group, clopidogrel metabolite concentrations in the clopidogrel/omeprazole group were significantly higher on Days 3 and 5. The concurrent administration of omeprazole and clopidogrel in healthy dogs was associated with an increase in the plasma concentration of an inactive metabolite of clopidogrel, but does not significantly alter the antiplatelet effects of clopidogrel.}, number={2}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Thames, B. E. and Lovvorn, J. and Papich, M. G. and Wills, R. and Archer, T. and Mackin, A. and Thomason, J.}, year={2017}, month={Apr}, pages={130–139} }
 @article{weese_giguère_guardabassi_morley_papich_ricciuto_sykes_2015, title={ACVIM Consensus Statement on Therapeutic Antimicrobial Use in Animals and Antimicrobial Resistance}, volume={29}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.12562}, DOI={10.1111/jvim.12562}, abstractNote={The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Weese, J.S. and Giguère, S. and Guardabassi, L. and Morley, P.S. and Papich, M. and Ricciuto, D.R. and Sykes, J.E.}, year={2015}, month={Mar}, pages={487–498} }
 @article{middleton_kubier_dirikolu_papich_mitchell_rubin_2016, title={Alternate-day dosing of itraconazole in healthy adult cats}, volume={39}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12231}, abstractNote={The current available formulations of itraconazole are not ideal for dosing in cats. The capsular preparation often does not allow for accurate dosing, the oral solution is difficult to administer and poorly tolerated, and the bioavailability of compounded formulations has been shown to be poor in other species. The aim of this study was to evaluate every other day dosing of 100 mg itraconazole capsule in healthy adult cats. Ten healthy adult cats received a 100 mg capsule of itraconazole orally every 48 h for 8 weeks. Peak and trough serum concentrations of itraconazole were measured weekly using high‐performance liquid chromatography (HPLC). Physical examination, complete blood count (CBC), and chemistry profiles were performed weekly. The dosage regimen achieved average therapeutic trough concentrations (>0.5 μg/mL) within 3 weeks. The protocol yielded no adverse effects in 8 of the 10 study cats, with affected cats recovering fully with discontinuation of the drug and supportive care. At 8 weeks, an average peak concentration of 1.79 ± 0.952 μg/mL (95% CI: 0.996–2.588) and an average trough concentration of 0.761 ± 0.540 μg/mL (95% CI: 0.314–1.216) were achieved. Overall, a 100 mg every other day oral dosage regimen for itraconazole in cats yielded serum concentrations with minimal fluctuation and with careful monitoring may be considered for treatment of cats with systemic fungal disease.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Middleton, S. M. and Kubier, A. and Dirikolu, L. and Papich, M. G. and Mitchell, M. A. and Rubin, S. I.}, year={2016}, month={Feb}, pages={27–31} }
 @article{bender_barlam_glore_gumley_grayzel_hoang_murphy_papich_sykes_watts_et al._2015, title={Antimicrobial stewardship in companion animal practice}, volume={246}, number={3}, journal={Journal of the American Veterinary Medical Association}, author={Bender, J. B. and Barlam, T. F. and Glore, R. P. and Gumley, N. and Grayzel, S. E. and Hoang, C. and Murphy, M. J. and Papich, M. G. and Sykes, J. E. and Watts, J. L. and et al.}, year={2015}, pages={287–288} }
 @article{papich_martinez_2015, title={Applying Biopharmaceutical Classification System (BCS) Criteria to Predict Oral Absorption of Drugs in Dogs: Challenges and Pitfalls}, volume={17}, ISSN={["1550-7416"]}, DOI={10.1208/s12248-015-9743-7}, abstractNote={The Biopharmaceutical Classification System (BCS) has been a prognostic tool for assessing the potential effects of formulation on the human drug oral bioavailability. When used in conjunction with in vitro dissolution tests, the BCS can support the prediction of in vivo product performance and the development of mechanistic models that support formulation assessments through the generation of “what if” scenarios. To date, the applicability of existing human BCS criteria has not been evaluated in dogs, thereby limiting its use in canine drug development. Therefore, we examined 50 drugs for which absolute bioavailability (F) was available both in dogs and humans. The drugs were also evaluated for any potential association between solubility (calculated from the dose number, Do) or lipophilicity (LogP) and F in dogs. In humans, solubility is determined in 250 mL of fluid. However, the appropriate volume for classifying drug solubility in dogs has not been established. In this analysis, the estimated volume of a water flush administered to fasted dogs (6 mL) and a volume of 250 mL scaled to a Beagle dog (35 mL) were examined. In addition, in humans, a Do value greater than 1.0 is used to define a compound as highly soluble and a LogP value greater than 1.72 as high permeability. These same criteria were applied for defining highly soluble and highly permeable in dogs. Whether using 35 or 6 mL to determine Do, the canine solubility classification remained unchanged for all but seven compounds. There were no clear associations between a drug’s F in dogs and humans or between the canine value of F and either its human BCS classification, its LogP value, or the canine Do estimate. There was a tendency for those drugs with canine values of F equal to or greater than 80% to have LogP values equal to or greater than 1.0. Exceptions to this observation tended to be those compounds known to be absorbed via mechanisms other than passive diffusion (e.g., via transporters or paracellular transporters). Although there are limitations to the approach used in this study, the results of our assessment strongly suggest that the human BCS classification system requires substantial modification before it can be reliably applied to dogs.}, number={4}, journal={AAPS JOURNAL}, author={Papich, Mark G. and Martinez, Marilyn N.}, year={2015}, month={Jul}, pages={948–964} }
 @article{messenger_wofford_papich_2016, title={Carprofen pharmacokinetics in plasma and in control and inflamed canine tissue fluid using in vivo ultrafiltration}, volume={39}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12233}, abstractNote={Measurement of unbound drug concentrations at their sites of action is necessary for accurate PK/PD modeling. The objective of this study was to determine the unbound concentration of carprofen in canine interstitial fluid (ISF) using in vivo ultrafiltration and to compare pharmacokinetic parameters of free carprofen concentrations between inflamed and control tissue sites. We hypothesized that active concentrations of carprofen would exhibit different dispositions in ISF between inflamed vs. normal tissues. Bilateral ultrafiltration probes were placed subcutaneously in six healthy Beagle dogs 12 h prior to induction of inflammation. Two milliliters of either 2% carrageenan or saline control was injected subcutaneously at each probe site, 12 h prior to intravenous carprofen (4 mg/kg) administration. Plasma and ISF samples were collected at regular intervals for 72 h, and carprofen concentrations were determined using HPLC. Prostaglandin E2 (PGE2) concentrations were quantified in ISF using ELISA. Unbound carprofen concentrations were higher in ISF compared with predicted unbound plasma drug concentrations. Concentrations were not significantly higher in inflamed ISF compared with control ISF. Compartmental modeling was used to generate pharmacokinetic parameter estimates, which were not significantly different between sites. Terminal half‐life (T½) was longer in the ISF compared with plasma. PGE2 in ISF decreased following administration of carprofen. In vivo ultrafiltration is a reliable method to determine unbound carprofen in ISF, and that disposition of unbound drug into tissue is much higher than predicted from unbound drug concentration in plasma. However, concentrations and pharmacokinetic parameter estimates are not significantly different in inflamed vs. un‐inflamed tissues.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Messenger, K. M. and Wofford, J. A. and Papich, M. G.}, year={2016}, month={Feb}, pages={32–39} }
 @article{apley_crist_fellner_gonzalez_hunter_martinez_messenheimer_modric_papich_parr_et al._2015, title={Determination of thermodynamic solubility of active pharmaceutical ingredients for veterinary species: A new USP general chapter}, volume={41}, number={3}, journal={Stimuli to the Revision Process. United States Pharmacopeia Pharmaceutical Forum}, author={Apley, M. and Crist, G.B. and Fellner, V. and Gonzalez, M.A. and Hunter, R.P. and Martinez, M.N. and Messenheimer, J.R. and Modric, S. and Papich, M.G. and Parr, A.F. and et al.}, year={2015} }
 @article{munana_nettifee-osborne_papich_2015, title={Effect of Chronic Administration of Phenobarbital, or Bromide, on Pharmacokinetics of Levetiracetam in Dogs with Epilepsy}, volume={29}, ISSN={["1939-1676"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84925714278&partnerID=MN8TOARS}, DOI={10.1111/jvim.12548}, abstractNote={BackgroundLevetiracetam (LEV) is a common add‐on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs.Hypothesis/ObjectivesTo evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs.AnimalsEighteen client‐owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB–BR group, n = 6).MethodsProspective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high‐pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area‐under‐the‐curve (AUC) calculated to the last measured time point.ResultsCompared to the PB and PB–BR groups, the BR group had significantly higher peak concentration (Cmax) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028).Conclusions and Clinical ImportanceConcurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add‐on treatment with phenobarbital in dogs.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Munana, K. R. and Nettifee-Osborne, J. A. and Papich, M. G.}, year={2015}, pages={614–619} }
 @article{hnot_cole_lorch_rajala-schultz_papich_2015, title={Effect of feeding on the pharmacokinetics of oral minocycline in healthy research dogs}, volume={26}, number={6}, journal={Veterinary Dermatology}, author={Hnot, M.L. and Cole, L.K. and Lorch, G. and Rajala-Schultz, P.J. and Papich, M.G.}, year={2015}, month={Dec}, pages={399–405} }
 @article{hnot_cole_lorch_papich_rajala-schultz_daniels_2015, title={Evaluation of canine- specific minocycline and doxycycline susceptibility breakpoints for meticillin-resistant Staphylococcus pseudintermedius isolates from dogs}, volume={26}, number={5}, journal={Veterinary Dermatology}, author={Hnot, M.L. and Cole, L.K. and Lorch, G. and Papich, M.G. and Rajala-Schultz, P.J. and Daniels, J.B.}, year={2015}, month={Oct}, pages={334–338} }
 @misc{papich_brown_kirk_2016, title={How to (properly) determine the beyond-use date and stability of a compounded formulation for pets}, volume={18}, ISSN={["1532-2750"]}, DOI={10.1177/1098612x15622518}, number={4}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Papich, Mark G. and Brown, Stacy and Kirk, Loren}, year={2016}, month={Apr}, pages={364–365} }
 @inbook{papich_messenger_2015, edition={5th}, title={Nonsteroidal anti-inflammatory drugs}, booktitle={Lumb & Jones' Veterinary Anesthesia and Analgesia}, publisher={Wiley Blackwell}, author={Papich, MG and Messenger, K}, editor={Grimm, K. and Lamont, LA and Tranquilli, W.J. and Greene, SA and Robertson, SAEditors}, year={2015}, pages={227–243} }
 @article{jacob_hoppin_steers_davis_davidson_hansen_lunn_murphy_papich_2015, title={Opinions of clinical veterinarians at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections}, volume={247}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.247.8.938}, DOI={10.2460/javma.247.8.938}, abstractNote={Abstract
Objective—To determine opinions of faculty members with clinical appointments, clinical veterinarians, residents, and interns at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections.
Design—Cross-sectional survey.
Sample—71 veterinarians.
Procedures—An online questionnaire was sent to all veterinarians with clinical service responsibilities at the North Carolina State University veterinary teaching hospital (n = 167). The survey included 23 questions regarding demographic information, educational experiences, current prescribing practices, and personal opinions related to antimicrobial selection, antimicrobial use, restrictions on antimicrobial use, and antimicrobial resistance.
Results—Of the 167 veterinarians eligible to participate, 71 (43%) responded. When respondents were asked to rate their level of concern (very concerned = 1; not concerned = 5) about antimicrobial-resistant infections, most (41/70 [59%]) assigned a score of 1, with mean score for all respondents being 1.5. Most survey participants rated their immediate colleagues (mean score, 1.9) as more concerned than other veterinary medical professionals (mean score, 2.3) and their clients (mean score, 3.4). Fifty-nine of 67 (88%) respondents felt that antimicrobials were overprescribed at the hospital, and 32 of 69 (46%) respondents felt uncomfortable prescribing at least one class of antimicrobials (eg, carbapenems or glycopeptides) because of public health concerns.
Conclusions and Clinical Relevance—Findings indicated that veterinarians at this teaching hospital were concerned about antimicrobial resistance, thought antimicrobials were overprescribed, and supported restricting use of certain antimicrobial classes in companion animals. Findings may be useful in educating future veterinarians and altering prescribing habits and antimicrobial distribution systems in veterinary hospitals.}, number={8}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Jacob, Megan E. and Hoppin, Jane A. and Steers, Nicola and Davis, Jennifer L. and Davidson, Gigi and Hansen, Bernie and Lunn, Katharine F. and Murphy, K. Marcia and Papich, Mark G.}, year={2015}, month={Oct}, pages={938–944} }
 @article{barbosa_johnson_papich_gulland_2015, title={PHARMACOKINETICS OF SINGLE-DOSE ORALLY ADMINISTERED CIPROFLOXACIN IN CALIFORNIA SEA LIONS (ZALOPHUS CALIFORNIANUS)}, volume={46}, ISSN={["1937-2825"]}, DOI={10.1638/2014-0159r.1}, abstractNote={Ciprofloxacin is commonly selected for clinical use due to its broad-spectrum efficacy and is a frequently administered antibiotic at The Marine Mammal Center, a marine mammal rehabilitation facility. Ciprofloxacin is used for treatment of California sea lions (Zalophus californianus) suffering from a variety of bacterial infections at doses extrapolated from other mammalian species. However, as oral absorption is variable both within and across species, a more accurate determination of appropriate dosage is needed to ensure effective treatment and avoid emergence of drug-resistant bacterial strains. A pharmacokinetic study was performed to assess plasma concentrations of ciprofloxacin in California sea lions after a single oral dose. Twenty healthy California sea lions received a single 10-mg/kg oral dose of ciprofloxacin administered in a herring fish. Blood was then collected at two of the following times from each individual: 0.5, 0.75, 1, 2, 4, 8, 10, 12, 18, and 24 hr postingestion. Plasma ciprofloxacin concentration was assessed via high-performance liquid chromatography. A population pharmacokinetics model demonstrated that an oral ciprofloxacin dose of 10 mg/kg achieved an area under the concentration vs. time curve of 6.01 μg hr/ml. Absorption was rapid, with ciprofloxacin detectable in plasma 0.54 hr after drug administration; absorption half-life was 0.09 hr. A maximum plasma concentration of 1.21 μg/ml was observed at 1.01 hr, with an elimination half-life of 3.09 hr. Ciprofloxacin administered orally at 10 mg/kg produced therapeutic antibacterial exposure for only some of the most susceptible bacterial organisms commonly isolated from California sea lions.}, number={2}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Barbosa, Lorraine and Johnson, Shawn P. and Papich, Mark G. and Gulland, Frances}, year={2015}, month={Jun}, pages={266–272} }
 @article{lemetayer_dowling_taylor_papich_2015, title={Pharmacokinetics and distribution of voriconazole in body fluids of dogs after repeated oral dosing}, volume={38}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12208}, abstractNote={The goal of this project was to determine the pharmacokinetics of voriconazole and its concentration in cerebrospinal fluid (CSF), aqueous humor, and synovial fluid in five healthy dogs following once daily oral dose of 6 mg⁄kg for 2 weeks. Body fluid and plasma drug concentrations were determined by high‐performance liquid chromatography (HPLC). Mild to moderate gastrointestinal adverse effects were seen. The mean AUC0–24: minimum inhibitory concentration (MIC) ratio was 15.23 for a chosen MIC of 1 μg/mL, which is lower than the recommended target of 20–25 and also lower than previously reported in dogs, perhaps reflecting induction of metabolizing enzymes by multiple dosing. Voriconazole concentrations in the CSF, aqueous humor, and synovial fluid were only 13–30% the concurrent plasma concentration, which is lower than previously reported in other species. Results of this study suggest that twice daily, administration may be necessary to maintain therapeutic plasma concentrations in dogs but further studies are warranted.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Lemetayer, J. D. and Dowling, P. M. and Taylor, S. M. and Papich, M. G.}, year={2015}, month={Oct}, pages={451–456} }
 @article{foster_jacob_warren_papich_2015, title={Pharmacokinetics of enrofloxacin and ceftiofur in plasma, interstitial fluid, and gastrointestinal tract of calves after subcutaneous injection, and bactericidal impacts on representative enteric bacteria}, volume={39}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12236}, DOI={10.1111/jvp.12236}, abstractNote={This study's objectives were to determine intestinal antimicrobial concentrations in calves administered enrofloxacin or ceftiofur sodium subcutaneously, and their impact on representative enteric bacteria. Ultrafiltration devices were implanted in the ileum and colon of 12 steers, which received either enrofloxacin or ceftiofur sodium. Samples were collected over 48 h after drug administration for pharmacokinetic/pharmacodynamic analysis. Enterococcus faecalis or Salmonella enterica (5 × 105 CFU/mL of each) were exposed in vitro to peak and tail (48 h postadministration) concentrations of both drugs at each location for 24 h to determine inhibition of growth and change in MIC. Enrofloxacin had tissue penetration factors of 1.6 and 2.5 in the ileum and colon, while ciprofloxacin, an active metabolite of enrofloxacin, was less able to cross into the intestine (tissue penetration factors of 0.7 and 1.7). Ceftiofur was rapidly eliminated leading to tissue penetration factors of 0.39 and 0.25. All concentrations of enrofloxacin were bactericidal for S. enterica and significantly reduced E. faecalis. Peak ceftiofur concentration was bactericidal for S. enterica, and tail concentrations significantly reduced growth. E. faecalis experienced growth at all ceftiofur concentrations. The MICs for both organisms exposed to peak and tail concentrations of antimicrobials were unchanged at the end of the study. Enrofloxacin and ceftiofur achieved intestinal concentrations capable of reducing intestinal bacteria, yet the short exposure of ceftiofur in the intestine may select for resistant organisms.}, number={1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Foster, D. M. and Jacob, M. E. and Warren, C. D. and Papich, M. G.}, year={2015}, month={May}, pages={62–71} }
 @article{tynan_papich_kerl_cohn_2016, title={Pharmacokinetics of minocycline in domestic cats}, volume={18}, ISSN={["1532-2750"]}, DOI={10.1177/1098612x15579114}, abstractNote={Objectives Recently, the increased cost and decreased availability of doxycycline has sparked an interest in using minocycline as an alternative. The purpose of this study was to determine the pharmacokinetics of minocycline in domestic cats in order to facilitate dosage decisions. Methods Purpose-bred, young adult cats were administered a single dose of either intravenous (IV; n = 4; 5 mg/kg) or oral (n = 6; 50 mg/cat) minocycline. Blood was collected from each at intervals up to 24 h afterwards. Minocycline was measured using high performance liquid chromatography with ultraviolet detection. A one-compartment pharmacokinetic model was fit to the oral data and a two-compartment model to the IV data via a computer program. Plasma protein binding was measured by fortifying blank plasma from untreated healthy cats with minocycline at two concentrations and applying an ultracentrifugation method. Results Two cats became transiently lethargic and tachypneic during IV drug infusion. One cat vomited 6.0 h after infusion, and two cats vomited either 1.5 h or ~5.0 h after oral drug administration. The mean oral dose administered was 13.9 ± 0.47 mg/kg. Oral bioavailability was approximately 62%. Plasma protein binding was 60% at 5 µg/ml and 46% at 1 μg/ml. After IV administration, elimination half-life (t½), apparent volume of distribution at steady-state, and systemic clearance were 6.7 h (coefficient of variation [CV] 14.4%), 1.5 l/kg (CV 34.5%) and 2.9 ml/kg/min (CV 40.8%), respectively. After oral administration the terminal t½ and peak concentration (Cmax) were 6.3 h (CV 9%) and 4.77 µg/ml (CV 36%), respectively. Conclusions and relevance Because most bacteria will have a minimum inhibitory concentration of ⩽0.5 μg/ml, an oral dose of 8.8 mg/kg q24h would be adequate to meet pharmacokinetic–pharmacodynamic targets after adjusting for protein binding. Although some gastrointestinal upset may occur, one 50 mg capsule orally q24h would provide appropriate dosing for most cats. }, number={4}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Tynan, Beth E. and Papich, Mark G. and Kerl, Marie E. and Cohn, Leah A.}, year={2016}, month={Apr}, pages={257–263} }
 @article{beaufrere_papich_brandao_nevarez_tully_2015, title={Plasma Drug Concentrations of Orally Administered Rosuvastatin in Hispaniolan Amazon Parrots (Amazona ventralis)}, volume={29}, ISSN={["1938-2871"]}, DOI={10.1647/2014-015}, abstractNote={Abstract Atherosclerotic diseases are common in pet psittacine birds, in particular Amazon parrots. While hypercholesterolemia and dyslipidemia have not definitely been associated with increased susceptibility to atherosclerosis in parrots, these are important and well-known risk factors in humans. Therefore statin drugs such as rosuvastatin constitute the mainstay of human treatment of dyslipidemia and the prevention of atherosclerosis. No pharmacologic studies have been performed in psittacine birds despite the high prevalence of atherosclerosis in captivity. Thirteen Hispaniolan Amazon parrots were used to test a single oral dose of 10 mg/kg of rosuvastatin with blood sampling performed according to a balanced incomplete block design over 36 hours. Because low plasma concentrations were produced in the first study, a subsequent pilot study using a dose of 25 mg/kg in 2 Amazon parrots was performed. Most plasma samples for the 10 mg/kg dose and all samples for the 25 mg/kg dose had rosuvastatin concentration below the limits of quantitation. For the 10 mg/kg study, the median peak plasma concentration and time to peak plasma concentration were 0.032 μg/mL and 2 hours, respectively. Our results indicate that rosuvastatin does not appear suitable in Amazon parrots as compounded and used at the dose in this study. Pharmacodynamic studies investigating lipid-lowering effects of statins rather than pharmacokinetic studies may be more practical and cost effective in future studies to screen for a statin with more ideal properties for potential use in psittacine dyslipidemia and atherosclerotic diseases.}, number={1}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Beaufrere, Hugues and Papich, Mark G. and Brandao, Joao and Nevarez, Javier and Tully, Thomas N., Jr.}, year={2015}, month={Mar}, pages={18–24} }
 @article{joudrey_robinson_kearney_papich_da cunha_2015, title={Plasma concentrations of lidocaine in dogs following lidocaine patch application over an incision compared to intact skin}, volume={38}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12224}, abstractNote={The objective was to compare plasma lidocaine concentrations when a commercially available 5% lidocaine patch was placed on intact skin vs. an incision. Our hypothesis was that greater absorption of lidocaine would occur from the incision site compared to intact skin. Ten dogs were used in a crossover design. A patch was placed over an incision, and then after a washout period, a patch was placed over intact skin. Plasma lidocaine concentrations were measured at patch placement; 20, 40 and 60 min; and 2, 4, 6, 12, 24, 36, 48, 72 and 96 h after patch placement. After patch removal, the skin was graded using a subjective skin reaction system. No dogs required rescue analgesia, and no toxicity or skin reaction was noted. Mean ± SD AUC and CMAX were 3054.29 ± 1095.93 ng·h/mL and 54.1 ± 15.84 ng/mL in the Incision Group, and 2269.9 ± 1037.08 ng·h/mL and 44.5 ± 16.34 ng/mL in the No‐Incision Group, respectively. The AUC was significantly higher in the Incision Group. The results of the study demonstrate that the actual body exposure to lidocaine was significantly higher when an incision was present compared to intact skin. No adverse effects were observed from either treatment. Efficacy was not evaluated.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Joudrey, S. D. and Robinson, D. A. and Kearney, M. T. and Papich, M. G. and Da Cunha, A. F.}, year={2015}, month={Dec}, pages={575–580} }
 @article{kendall_papich_2015, title={Posaconazole pharmacokinetics after administration of an intravenous solution, oral suspension, and delayed-release tablet to dogs}, volume={76}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.76.5.454}, abstractNote={Abstract
OBJECTIVE To determine pharmacokinetics of posaconazole in dogs given an IV solution, oral suspension, and delayed-release tablet.
ANIMALS 6 healthy dogs.
PROCEDURES Posaconazole was administered IV (3 mg/kg) and as an oral suspension (6 mg/kg) to dogs in a randomized crossover study. Blood samples were collected before (time 0) and for 48 hours after each dose. In an additional experiment, 5 of the dogs received posaconazole delayed-release tablets (mean dose, 6.9 mg/kg); blood samples were collected for 96 hours. Plasma concentrations were analyzed with high-performance liquid chromatography.
RESULTS IV solution terminal half-life (t1/2) was 29 hours (coefficient of variation [CV], 23%). Clearance and volume of distribution were 78 mL/h/kg (CV, 59%) and 3.3 L/kg (CV, 38%), respectively. Oral suspension t1/2 was 24 hours (CV, 42%). Maximum plasma concentration (Cmax) of 0.42 μg/mL (CV, 56%) was obtained at 7.7 hours (CV, 92%). Mean bioavailability was 26% (range, 7.8% to 160%). Delayed-release tablet t1/2 was 42 hours (CV, 25%), with a Cmax of 1.8 μg/mL (CV, 44%) at 9.5 hours (CV, 85%). Mean bioavailability of tablets was 159% (range, 85% to 500%). Bioavailability of delayed-release tablets was 497% (range, 140% to 1,800%) relative to that of the oral suspension.
CONCLUSIONS AND CLINICAL RELEVANCE Absorption of posaconazole oral suspension in dogs was variable. Absorption of the delayed-release tablets was greater than absorption of the oral suspension, with a longer t1/2 that may favor its clinical use in dogs. Administration of delayed-release tablets at a dosage of 5 mg/kg every other day can be considered for future studies.}, number={5}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Kendall, Jennifer and Papich, Mark G.}, year={2015}, month={May}, pages={454–459} }
 @article{bender_barlam_glore_gumley_grayzel_hoang_murphy_papich_sykes_watts_et al._2015, title={The AVMA Task Force for Antimicrobial Stewardship in Companion Animal Practice responds}, volume={246}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Bender, J.B. and Barlam, T.F. and Glore, R.P. and Gumley, N. and Grayzel, S.E. and Hoang, C. and Murphy, M.J. and Papich, M.G. and Sykes, J.E. and Watts, J.L. and et al.}, year={2015}, month={Apr}, pages={727–8} }
 @misc{bender_barlam_glore_gumley_grayzel_hoang_murphy_papich_sykes_watts_et al._2015, title={The AVMA task force for antimicrobial stewardship in companion animal practice responds}, volume={246}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Bender, J. B. and Barlam, T. F. and Glore, R. P. and Gumley, N. and Grayzel, S. E. and Hoang, C. and Murphy, M. J. and Papich, M. G. and Sykes, J. E. and Watts, J. L. and et al.}, year={2015}, pages={727–728} }
 @article{grayzel_bender_glore_gumley_sykes_whichard_papich_watts_barlam_murphy_et al._2015, title={Understanding companion animal practitioners' attitudes toward antimicrobial stewardship}, volume={247}, number={8}, journal={Journal of the American Veterinary Medical Association}, author={Grayzel, S. E. and Bender, J. B. and Glore, R. P. and Gumley, N. and Sykes, J. E. and Whichard, J. M. and Papich, M. G. and Watts, J. L. and Barlam, T. F. and Murphy, M. J. and et al.}, year={2015}, pages={883–884} }
 @inbook{papich_2014, title={Consulting Editor, Appendix I, Table of Common Drugs: Approximate Dosages}, booktitle={Kirk’s Current Veterinary Therapy XV}, publisher={Saunders- Elsevier}, author={Papich, M.G.}, editor={Bonagura, JD and Twedt, DCEditors}, year={2014}, pages={1307–1335} }
 @article{slate_bandyopadhyay_francis_papich_karolewski_hod_prestia_2014, title={Efficacy of enrofloxacin in a mouse model of sepsis}, volume={53}, number={4}, journal={Journal of the American Association for Laboratory Animal Science}, author={Slate, A. R. and Bandyopadhyay, S. and Francis, K. P. and Papich, M. G. and Karolewski, B. and Hod, E. A. and Prestia, K. A.}, year={2014}, pages={381–386} }
 @article{parkinson_tolbert_messenger_odunayo_brand_davidson_peters_reed_papich_2015, title={Evaluation of the Effect of Orally Administered Acid Suppressants on Intragastric pH in Cats}, volume={29}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.12493}, abstractNote={BackgroundAcid suppressant drugs are a mainstay of treatment for cats with gastrointestinal erosion and ulceration. However, clinical studies have not been performed to compare the efficacy of commonly PO administered acid suppressants in cats.Hypothesis/ObjectivesTo compare the effect of PO administered famotidine, fractionated omeprazole tablet (fOT), and omeprazole reformulated paste (ORP) on intragastric pH in cats. We hypothesized that both omeprazole formulations would be superior to famotidine and placebo.AnimalsSix healthy adult DSH colony cats.MethodsUtilizing a randomized, 4‐way crossover design, cats received 0.88–1.26 mg/kg PO q12h fOT, ORP, famotidine, and placebo (lactose capsules). Intragastric pH monitoring was used to continuously record intragastric pH for 96 hours beginning on day 4 of treatment. Plasma omeprazole concentrations at steady state (day 7) were determined by high performance liquid chromatography (HPLC) with ultraviolet detection. Mean percentage time that intragastric pH was ≥3 and ≥4 were compared among groups using ANOVA with a posthoc Tukey‐Kramer test (α = 0.05).ResultsThe mean percentage time ± SD that intragastric pH was ≥3 was 68.4 ± 35.0% for fOT, 73.9 ± 23.2% for ORP, 42.8 ± 18.6% for famotidine, and 16.0 ± 14.2% for placebo. Mean ± SD plasma omeprazole concentrations were similar in cats receiving fOT compared to those receiving ORP and in a range associated with acid suppression reported in other studies.Conclusions and Clinical ImportanceThese results suggest that both omeprazole formulations provide superior acid suppression in cats compared to famotidine or placebo. Fractionated enteric‐coated OT is an effective acid suppressant despite disruption of the enteric coating.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Parkinson, S. and Tolbert, K. and Messenger, K. and Odunayo, A. and Brand, M. and Davidson, G. and Peters, E. and Reed, A. and Papich, M. G.}, year={2015}, pages={104–112} }
 @misc{hillier_lloyd_weese_blondeau_boothe_breitschwerdt_guardabassi_papich_rankin_turnidge_et al._2014, title={Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases)}, volume={25}, number={3}, journal={Veterinary Dermatology}, author={Hillier, A. and Lloyd, D. H. and Weese, J. S. and Blondeau, J. M. and Boothe, D. and Breitschwerdt, E. and Guardabassi, L. and Papich, M. G. and Rankin, S. and Turnidge, J. D. and et al.}, year={2014}, pages={163-} }
 @article{hillier_lloyd_weese_blondeau_boothe_breitschwerdt_guardabassi_papich_rankin_turnidge_et al._2014, title={Guidelines for the diagnosis and antimicrobial therapy of canine superficial bacterial folliculitis (Antimicrobial Guidelines Working Group of the International Society for Companion Animal Infectious Diseases)}, volume={25}, number={3}, journal={Veterinary Dermatology}, author={Hillier, A. and Lloyd, D.H. and Weese, J.S. and Blondeau, J.M. and Boothe, D. and Breitschwerdt, E. and Guardabassi, L. and Papich, M.G. and Rankin, S. and Turnidge, J.D. and et al.}, year={2014}, month={Jun}, pages={163–75} }
 @article{warren_prange_campbell_gerard_martin_jacob_smith_papich_foster_2014, title={Implantation of an ultrafiltration device in the ileum and spiral colon of steers to continuously collect intestinal fluid}, volume={97}, ISSN={0034-5288}, url={http://dx.doi.org/10.1016/j.rvsc.2014.10.012}, DOI={10.1016/j.rvsc.2014.10.012}, abstractNote={Collection of fluid from the lumen of the gastrointestinal tract is commonly necessary for research projects, but presents challenges including intestinal motility and potential for leakage of intestinal contents. In this study, ultrafiltration collection devices were surgically implanted in the ileum and spiral colon of 12 steers for repeated collection of intestinal fluid over 48 hours. There were no significant complications associated with surgery or during the post-operative period, nor were there any significant pathologic changes found at necropsy 3 or 4 days post-surgery. Over 48 hours, we obtained 88% of the desired 212 samples. Only two devices failed to routinely collect samples. Use of ultrafiltration probes is a novel, consistent and humane method to repeatedly sample the gastrointestinal contents.}, number={3}, journal={Research in Veterinary Science}, publisher={Elsevier BV}, author={Warren, Chelsea D. and Prange, Timo and Campbell, Nigel B. and Gerard, Mat P. and Martin, Luke G. and Jacob, Megan E. and Smith, Geof W. and Papich, Mark G. and Foster, Derek M.}, year={2014}, month={Dec}, pages={611–615} }
 @article{chinnadurai_messenger_papich_harms_2014, title={Meloxicam pharmacokinetics using nonlinear mixed-effects modeling in ferrets after single subcutaneous administration}, volume={37}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12099}, DOI={10.1111/jvp.12099}, abstractNote={This study was designed to investigate the pharmacokinetics of meloxicam, an oxicam class, nonsteroidal anti‐inflammatory drug (NSAID), in ferrets. We determined the pharmacokinetic properties of a single subcutaneous dose of meloxicam (0.2 mg/kg) in nine male and nine female ferrets. Blood samples were collected by venipuncture of the cranial vena cava into heparinized syringes. Plasma meloxicam concentrations were determined by high‐pressure liquid chromatography (HPLC). Pharmacokinetic variables were calculated using nonlinear mixed‐effects modeling to take advantage of the population‐based sampling scheme and to minimize sample volume collected per animal. Maximum plasma concentration, volume of distribution per absorption, and elimination half‐life were 0.663 μg/mL, 0.21 L, and 11.4 h, respectively, for females and 0.920 μg/mL, 0.35 L, and 17.8 h, respectively, for males. Significant differences were found in each of the above parameters between male and female ferrets. Systemic clearance per absorption was not affected by gender and was 13.4 mL/h. Analgesic efficacy was not evaluated, but plasma meloxicam concentrations achieved in these animals are considered effective in other species. Sex differences in the pharmacokinetic behavior of meloxicam should be taken into consideration when treating ferrets.}, number={4}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Chinnadurai, S. K. and Messenger, K. M. and Papich, M. G. and Harms, C. A.}, year={2014}, month={Feb}, pages={382–387} }
 @article{maaland_guardabassi_papich_2014, title={Minocycline pharmacokinetics and pharmacodynamics in dogs: dosage recommendations for treatment of meticillin-resistant Staphylococcus pseudintermedius
 infections}, volume={25}, ISSN={0959-4493}, url={http://dx.doi.org/10.1111/vde.12130}, DOI={10.1111/vde.12130}, abstractNote={BackgroundAlthough minocycline is not licensed for use in dogs, this tetracycline has therapeutic potential against meticillin‐resistant Staphylococcus pseudintermedius.Hypothesis/ObjectivesThe aim of this study was to establish rational dosage recommendations for minocycline use in dogs. Specific objectives were to generate and analyse minocycline pharmacokinetic (PK) data on plasma and interstitial fluid (ISF) concentrations, plasma protein binding and pharmacodynamic (PD) data on antimicrobial activity against S. pseudintermedius.AnimalsSix healthy dogs from a research colony were used in this study.MethodsDogs were administered 5 mg/kg intravenously and 10 mg/kg orally (p.o.) of minocycline hydrochloride in separate crossover experiments. In vivo drug concentrations in plasma and in ISF collected by ultrafiltration were measured by high‐performance liquid chromatography. Pharmacokinetic analysis was performed on plasma and ISF concentrations. PK/PD analysis was completed using in vitro data on plasma protein binding and minocycline susceptibility in 168 S. pseudintermedius isolates.ResultsMinocycline distributed to the ISF to a higher degree than predicted by the protein‐unbound fraction in plasma. A large volume of distribution after oral administration, with plasma and ISF elimination half‐lives of 4.1 and 7.4 h, respectively, demonstrated that the ISF serves as a drug reservoir for sustained tissue concentrations. Monte Carlo simulation, used to assess target attainment at different drug dosages, indicated that p.o. administration of 5 mg/kg twice daily is sufficient to inhibit S. pseudintermedius strains with minimal inhibitory concentrations ≤0.25 μg/mL.Conclusions and clinical importanceBesides dosage recommendations for therapy of meticillin‐resistant Staphylococcus pseudintermedius infections in dogs, the study also provides PK/PD data necessary to consider species‐specific clinical breakpoints for minocycline susceptibility testing.}, number={3}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Maaland, Marit G. and Guardabassi, Luca and Papich, Mark G.}, year={2014}, month={May}, pages={182–e47} }
 @article{simeone_nollens_meegan_schmitt_jensen_papich_smith_2014, title={PHARMACOKINETICS OF SINGLE DOSE ORAL MELOXICAM IN BOTTLENOSE DOLPHINS (TURSIOPS TRUNCATUS)}, volume={45}, ISSN={["1937-2825"]}, DOI={10.1638/2013-0281r1.1}, abstractNote={Abstract:  The objective of this study was to investigate the pharmacokinetics of meloxicam in bottlenose dolphins (Tursiops truncatus). Ten adult bottlenose dolphins were used for the study. Each animal received a single oral dose of meloxicam at 0.1 mg/kg. Two to seven serial blood samples were collected per animal, at one of fourteen time points between T = 0 and T = 240 hr. Complete blood count and serum chemistry analysis were performed prior to drug administration, as well as at the final time point for each individual. Plasma drug concentrations were determined by high-pressure liquid chromatography. No adverse hematological, biochemical or clinical changes were noted during the study period. After oral administration, a peak plasma concentration of 1.03 μg/mL was achieved at approximately 11 hr. This suggests that a single oral dose of 0.1 mg/kg provides a peak plasma level similar to what is considered therapeutic in other species. However, the elimination of meloxicam in cetaceans was slower than in other species, with an elimination half-life of almost 70 hr, and detectable drug concentrations up to 7 days. A single oral dose of 0.1 mg/kg appears safe for use in this species, but caution in repeated dosing must be used, due to the prolonged elimination, until multi-dose pharmacokinetic studies are determined.}, number={3}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Simeone, Claire A. and Nollens, Hendrik H. and Meegan, Jenny M. and Schmitt, Todd L. and Jensen, Eric D. and Papich, Mark G. and Smith, Cynthia R.}, year={2014}, month={Sep}, pages={594–599} }
 @article{papich_2014, title={Pharmacokinetic-pharmacodynamic (PK-PD) modeling and the rational selection of dosage regimes for the prudent use of antimicrobial drugs}, volume={171}, ISSN={["1873-2542"]}, DOI={10.1016/j.vetmic.2013.12.021}, abstractNote={One of the strategies to decrease inappropriate antimicrobial use in veterinary medicine is to apply pharmacokinetic-pharmacodynamic (PK-PD) principles to dosing regimens. If antimicrobials are used appropriately by applying these principles to attain targets for area-under-the-curve to MIC ratio (AUC/MIC), peak concentration to MIC ratio (CMAX/MIC), and time above MIC (T>MIC), more effective antibiotic therapy is possible, thus avoiding ineffective administration. Another mechanism whereby inappropriate antibiotic administration can be avoided is to use accurate Interpretive Criteria established by the Clinical Laboratory Standards Institute (CLSI) for breakpoint selection. Inaccurate breakpoints will encourage antibiotic administration that is likely to be ineffective. For newly approved antimicrobials, three criteria are used for determining breakpoints: PK-PD criteria, MIC distributions, and clinical response. For older (often generic drugs) evaluated by the CLSI, recent clinical data may not be available and breakpoints are derived from PK-PD principles, wild-type distributions, and Monte Carlo simulations. It is the goal of the CLSI subcommittee that these revised breakpoints will encourage more effective antimicrobial use and avoid unnecessary antimicrobial administration.}, number={3-4}, journal={VETERINARY MICROBIOLOGY}, author={Papich, Mark G.}, year={2014}, month={Jul}, pages={480–486} }
 @article{papich_2014, title={Pharmacokinetic-pharmacodynamic values for amoxicillin in pigs}, volume={75}, DOI={10.2460/ajvr.75.4.316}, number={4}, journal={American Journal of Veterinary Research}, author={Papich, M.G.}, year={2014}, month={Apr}, pages={316} }
 @article{hunyadi_papich_pusterla_2015, title={Pharmacokinetics of a low dose and FDA-labeled dose of diclazuril administered orally as a pelleted topdressing in adult horses}, volume={38}, DOI={10.1111/jvp.12176}, abstractNote={The purpose of this study was to determine the pharmacokinetics of the FDA‐approved labeled dose of diclazuril and compare it to a low dose in plasma and CSF in adult horses. During each research period, six healthy adult horses received 0.5 mg/kg of 1.56% diclazuril pellets (ProtazilTM, Merck Animal Health) compared to the approved labeled dose of 1 mg/kg orally once in two separate phases. A dose of 0.5 mg/kg was calculated to each horse's weight. Blood was then collected immediately before diclazuril administration and then at regular intervals up to a 168 h. After the last blood collection following the single dose at hour 168, a once daily oral dose was administered for the next 10 days to ensure the drug's concentration reached steady‐state. To determine the CSF concentration at steady‐state, CSF samples were collected after the 9th oral dose. Blood was then collected after the 10th dose and then at regular intervals up to 168 h. A washout period of 4 weeks was allowed before repeating this protocol for the FDA‐labeled dose at 1 mg/kg. Plasma and CSF samples were analyzed by high‐pressure liquid chromatography. A one‐compartment pharmacokinetic model with first‐order oral absorption was fitted to the single administration data. Steady‐state pharmacokinetics was performed using noncompartmental analysis for steady‐state analysis. The mean (standard deviation) concentration of diclazuril in CSF following the low dose was 26 ng/mL (5 ng/mL), while CSF in the FDA‐labeled dose was 25 ng/mL (4 ng/mL), P = 0.3750. Substantial accumulation in plasma occurred at steady‐state after the 10th dose for both doses. The results of this study show that diclazuril pellets given at the approved label dose and a lower dose both produce similar plasma drug concentrations at steady‐state and attain plasma and CSF concentrations known to inhibit Sarcocystis neurona in cell culture.}, number={3}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Hunyadi, L. and Papich, Mark and Pusterla, N.}, year={2015}, pages={243–248} }
 @inbook{hawkins_papich_2014, title={Respiratory drug therapy}, booktitle={Kirk’s Current Veterinary Therapy XV}, publisher={Saunders-Elsevier}, author={Hawkins, EC and Papich, MG}, editor={Bonagura, JD and Twedt, DCEditors}, year={2014}, pages={622–628} }
 @article{lloyd_weese_blondeau_boothe_breitschwerdt_guardabassi_papich_rankin_turnidge_sykes_et al._2014, title={Response to letter from J Mottet “Comments on the ISCAID Guidelines on the use of antimicrobial therapies in canine superficial bacterial folliculitis”}, volume={25}, ISSN={0959-4493}, url={http://dx.doi.org/10.1111/vde.12167}, DOI={10.1111/vde.12167}, abstractNote={Rabies remains a burden in Africa, disproportionately affecting the most vulnerable despite the availability of effective vaccines.Nigeria, the most populous African country, needs rapid disease control actions and commitments to achieve the goal of eliminating dog-mediated rabies by 2030.Surveillance is an essential element of effective disease control strategies.This study examined the current state of operationality of the rabies surveillance system for early case detection and management in Gombe state, Nigeria, through a One Health lens.It further examined the barriers impeding the effectiveness of the surveillance based on the perception of surveillance workers.Qualitative and quantitative methods were used to assess the structure of the system and its functioning.Data on dog bite and rabid cases obtained from the veterinary services in Gombe state were analysed descriptively.A total of 13 key informants were interviewed using a semi-structured interview guide.Qualitative data were analysed using thematic analysis to explore in depth the factors that influenced the operationality of the system.A total of 157 potential human exposures to rabies were identified in this study, out of which two people reportedly died at the health facility after showing symptoms highly suggestive of rabies.In terms of rabies surveillance and control, cross-sectoral collaboration was found between the human health and veterinary sectors for risk assessment of potential rabies exposures and its management.Some identified factors affecting the operations of the surveillance were inadequate funding, lack of infrastructure, lack of feedback from higher authorities and insufficient knowledge of rabies prevention and management.To improve the capacity for case detection and management within the state, the appropriate authorities may focus on increasing awareness about the disease to the populace to increase the number of cases identified by the system, employ more workers and strengthen the surveillance capability of existing workers.}, number={6}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Lloyd, David H. and Weese, J. Scott and Blondeau, Joseph M. and Boothe, Dawn and Breitschwerdt, Edward and Guardabassi, Luca and Papich, Mark and Rankin, Shelley and Turnidge, John D. and Sykes, Jane E. and et al.}, year={2014}, month={Aug}, pages={567–568} }
 @inbook{papich_2015, title={Strategies for Treating Infections in Critically Ill Patients}, ISBN={9781455703067}, url={http://dx.doi.org/10.1016/b978-1-4557-0306-7.00182-3}, DOI={10.1016/b978-1-4557-0306-7.00182-3}, booktitle={Small Animal Critical Care Medicine}, publisher={Elsevier}, author={Papich, Mark G.}, year={2015}, pages={949–955} }
 @article{martinez_blondeau_cerniglia_fink-gremmels_guenther_hunter_li_papich_silley_soback_et al._2014, title={Workshop report: The 2012 Antimicrobial Agents in Veterinary Medicine: exploring the consequences of antimicrobial drug use: a 3-D approach}, volume={37}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12104}, abstractNote={Antimicrobial resistance is a global challenge that impacts both human and veterinary health care. The resilience of microbes is reflected in their ability to adapt and survive in spite of our best efforts to constrain their infectious capabilities. As science advances, many of the mechanisms for microbial survival and resistance element transfer have been identified. During the 2012 meeting of Antimicrobial Agents in Veterinary Medicine (AAVM), experts provided insights on such issues as use vs. resistance, the available tools for supporting appropriate drug use, the importance of meeting the therapeutic needs within the domestic animal health care, and the requirements associated with food safety and food security. This report aims to provide a summary of the presentations and discussions occurring during the 2012 AAVM with the goal of stimulating future discussions and enhancing the opportunity to establish creative and sustainable solutions that will guarantee the availability of an effective therapeutic arsenal for veterinary species.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Martinez, M. and Blondeau, J. and Cerniglia, C. E. and Fink-Gremmels, J. and Guenther, S. and Hunter, R. P. and Li, X. -Z. and Papich, M. and Silley, P. and Soback, S. and et al.}, year={2014}, month={Feb}, pages={E1–E16} }
 @inbook{sykes_papich_2014, title={Antibacterial Drugs}, ISBN={9781437707953}, url={http://dx.doi.org/10.1016/b978-1-4377-0795-3.00008-9}, DOI={10.1016/b978-1-4377-0795-3.00008-9}, booktitle={Canine and Feline Infectious Diseases}, publisher={Elsevier}, author={Sykes, Jane E. and Papich, Mark G.}, year={2014}, pages={66–86} }
 @article{papich_2013, title={Antibiotic Treatment of Resistant Infections in Small Animals}, volume={43}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/j.cvsm.2013.04.006}, DOI={10.1016/j.cvsm.2013.04.006}, abstractNote={There are few veterinary clinical studies to support a recommended use and dose for treating resistant bacterial infections in small animals. Resistance against many common antibiotics is possible and a susceptibility test is advised. Infections caused by Pseudomonas aeruginosa presents a special problem. Staphylococcus isolated from small animals is most likely to be Staphylococcus pseudintermedius. The most important resistance mechanism for Staphylococcus is methicillin resistance. The only antimicrobials to which some gram-negative bacilli are sensitive may be extended-spectrum cephalosporins, carbapenems (penems), selected penicillin derivatives, amikacin, or tobramycin. A susceptibility test is needed to identify the appropriate drug for these infections.}, number={5}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Papich, Mark G.}, year={2013}, month={Sep}, pages={1091–1107} }
 @inbook{sykes_papich_2014, title={Antifungal Drugs}, ISBN={9781437707953}, url={http://dx.doi.org/10.1016/b978-1-4377-0795-3.00009-0}, DOI={10.1016/b978-1-4377-0795-3.00009-0}, booktitle={Canine and Feline Infectious Diseases}, publisher={Elsevier}, author={Sykes, Jane E. and Papich, Mark G.}, year={2014}, pages={87–96} }
 @inbook{papich_2013, place={St. Louis, Missouri}, title={Antimicrobial drugs}, booktitle={Canine and Feline Gastroenterology}, publisher={Elsevier Saunders}, author={Papich, M.G.}, editor={Washabau, R.J. and Day, M.J.Editors}, year={2013}, pages={471–476} }
 @article{papich_2013, title={Antimicrobials, Susceptibility Testing, and Minimum Inhibitory Concentrations (MIC) in Veterinary Infection Treatment}, volume={43}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/j.cvsm.2013.04.005}, DOI={10.1016/j.cvsm.2013.04.005}, abstractNote={Veterinarians are quick to attribute an unsuccessful antimicrobial treatment to a failure of the culture and susceptibility test. There are many reasons why antimicrobial treatment fails. When evaluating a patient that has failed to respond to therapy, one must consider any of the many factors that contribute to antibiotic failure.}, number={5}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Papich, Mark G.}, year={2013}, month={Sep}, pages={1079–1089} }
 @inbook{sykes_papich_2014, title={Antiprotozoal Drugs}, ISBN={9781437707953}, url={http://dx.doi.org/10.1016/b978-1-4377-0795-3.00010-7}, DOI={10.1016/b978-1-4377-0795-3.00010-7}, booktitle={Canine and Feline Infectious Diseases}, publisher={Elsevier}, author={Sykes, Jane E. and Papich, Mark G.}, year={2014}, pages={97–104} }
 @inbook{sykes_papich_2014, title={Antiviral and Immunomodulatory Drugs}, ISBN={9781437707953}, url={http://dx.doi.org/10.1016/b978-1-4377-0795-3.00007-7}, DOI={10.1016/b978-1-4377-0795-3.00007-7}, booktitle={Canine and Feline Infectious Diseases}, publisher={Elsevier}, author={Sykes, Jane E. and Papich, Mark G.}, year={2014}, pages={54–65} }
 @article{flammer_massey_roudybush_meek_papich_2013, title={Assessment of Plasma Concentrations and Potential Adverse Effects of Doxycycline in Cockatiels (Nymphicus hollandicus) Fed a Medicated Pelleted Diet}, volume={27}, ISSN={["1938-2871"]}, DOI={10.1647/1082-6742-27.3.187}, abstractNote={Doxycycline hyclate was mixed with soybean oil and then added to a low-fat pelleted diet that contained approximately 2.4% fat, which produced a final diet that contained a calculated 6.4% fat and 300 mg doxycycline per kilogram of diet. The medicated diet was fed to 9 healthy adult cockatiels (Nymphicus hollandicus) for 47 days; a control group of 6 birds received the identical diet without doxycycline. Trough doxycycline plasma concentrations were measured 7 times during treatment and ranged from 0.98 to 3.83 microg/mL with an overall median of 2.09 microg/ mL. The birds were observed daily, weighed, and examined at least weekly, and selected plasma biochemical parameters were measured before treatment and at days 21 and 42. No adverse effects were noted, except one treatment bird became obese. This medicated diet may be suitable for treating spiral bacteria and Chlamydophila psittaci infections in cockatiels that will consume a pelleted diet.}, number={3}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Flammer, Keven and Massey, J. Gregory and Roudybush, Tom and Meek, Caroline J. and Papich, Mark G.}, year={2013}, month={Sep}, pages={187–193} }
 @article{mawby_whittemore_genger_papich_2014, title={Bioequivalence of Orally Administered Generic, Compounded, and Innovator-Formulated Itraconazole in Healthy Dogs}, volume={28}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.12219}, abstractNote={BackgroundItraconazole is commonly used to treat systemic fungal infections in dogs, but problems exist with absorption and cost.ObjectiveTo determine oral bioequivalence of generic and compounded itraconazole compared to original innovator (brand name) itraconazole in healthy dogs.AnimalsNine healthy, adult research Beagle dogs.MethodsA randomized, 3‐way, 3‐period, crossover design with an 8‐day washout period. After a 12‐hour fast, each dog received 100 mg (average: 10.5 mg/kg) of either innovator itraconazole, an approved human generic capsule, or compounded itraconazole (compounded using a commercially available compounding vehicle) with a small meal. Plasma was collected at predetermined intervals for high pressure liquid chromatography analysis. Concentration data were analyzed using noncompartmental pharmacokinetics to determine area under the curve (AUC), peak concentration (CMAX), and terminal half‐life. Bioequivalence tests compared generic and compounded itraconazole to the reference formulation.ResultsAverage ratios of compounded and generic formulations to the reference formulation of itraconazole for AUC were 5.52% and 104.2%, respectively, and for CMAX were 4.14% and 86.34%, respectively. A test of bioequivalence using 2 one‐sided tests and 90% confidence intervals did not meet bioequivalence criteria for either formulation.Conclusion and Clinical ImportanceNeither generic nor compounded itraconazole is bioequivalent to the reference formulation in dogs. However, pharmacokinetic data for generic formulation were similar enough that therapeutic concentrations could be achieved. Compounded itraconazole produced such low plasma concentrations, it is unlikely to be effective; therefore, compounded itraconazole should not be used in dogs.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Mawby, D. I. and Whittemore, J. C. and Genger, S. and Papich, M. G.}, year={2014}, month={Jan}, pages={72–77} }
 @article{papich_davidson_fortier_2013, title={Doxycycline concentration over time after storage in a compounded veterinary preparation}, volume={242}, ISSN={["1943-569X"]}, DOI={10.2460/javma.242.12.1674}, abstractNote={Abstract
Objective—To determine the concentration of doxycycline compounded from doxycycline hyclate tablets into liquid formulations for oral administration in veterinary species and stored for 28 days.
Design—Evaluation study.
Sample—Doxycycline hyclate tablets (100 mg) crushed and mixed with a 50:50 mixture of syrup and suspension vehicles for oral administration to produce 3 batches each of 2 doxycycline formulations: 33.3 and 166.7 mg/mL.
Procedures—Formulations were stored, protected from light, at room temperature (22° to 26°C [71.6° to 78.8°F]) and at a controlled cold temperature (refrigerated 2° to 8°C [35.6° to 46.4°F]). Doxycycline was extracted from the formulations, and concentration was measured by high-pressure liquid chromatography on days 0 (date of preparation), 1, 4, 7, 14, 21, and 28. Concentrations were compared with those of a US Pharmacopeial Convention reference standard. Formulation quality at each point was also assessed through color change, formulation consistency, and suspension uniformity.
Results—On days 0, 1, 4, and 7, the concentration of each formulation was within 90% to 110% of the reference standard (range, 93% to 109%), which was deemed acceptable. However, doxycycline concentrations had decreased dramatically by day 14 and remained low for the duration of the study period. Doxycycline concentrations on days 14, 21, and 28 were all < 20% (range, 14% to 18%) of the reference standard, and the quality of the formulations decreased as well. No effect of storage temperatures on doxycycline concentration was identified.
Conclusions and Clinical Relevance—The concentration of doxycycline, compounded from commercial tablets in the vehicles evaluated to yield doses of 33.3 and 166.7 mg/mL, cannot be assured beyond 7 days.}, number={12}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Papich, Mark G. and Davidson, Gigi S. and Fortier, Lisa A.}, year={2013}, month={Jun}, pages={1674–1678} }
 @inbook{papich_2013, place={Gloucester}, edition={4th}, title={Drug therapy for diseases of the central nervous system}, booktitle={BSAVA Manual of Canine and Feline Neurology}, publisher={British Small Animal Veterinary Association}, author={Papich, M.G.}, editor={Platt, S.R. and Olby, N.J.Editors}, year={2013}, pages={452–469} }
 @article{papich_2013, title={Identifying antimicrobial resistance}, volume={243}, number={11}, journal={Journal of the American Veterinary Medical Association}, author={Papich, M.G.}, year={2013}, month={Jan}, pages={1517–1518} }
 @article{maaland_papich_turnidge_guardabassi_2013, title={Pharmacodynamics of Doxycycline and Tetracycline against Staphylococcus pseudintermedius: Proposal of Canine-Specific Breakpoints for Doxycycline}, volume={51}, ISSN={["1098-660X"]}, DOI={10.1128/jcm.01498-13}, abstractNote={ABSTRACT
          
            Doxycycline is a tetracycline that has been licensed for veterinary use in some countries, but no clinical breakpoints are available for veterinary pathogens. The objectives of this study were (i) to establish breakpoints for doxycycline and (ii) to evaluate the use of tetracycline as a surrogate to predict the doxycycline susceptibility of
            Staphylococcus pseudintermedius
            isolates. MICs and inhibition zone diameters were determined for 168 canine
            S. pseudintermedius
            isolates according to Clinical and Laboratory Standards Institute (CLSI) standards. Tetracycline resistance genes were detected by PCR, and time-kill curves were determined for representative strains.
            In vitro
            pharmacodynamic and target animal pharmacokinetic data were analyzed by Monte Carlo simulation (MCS) for the development of MIC interpretive criteria. Optimal zone diameter breakpoints were defined using the standard error rate-bounded method. The two drugs displayed bacteriostatic activity and bimodal MIC distributions. Doxycycline was more active than tetracycline in non-wild-type strains. MCS and target attainment analysis indicated a certainty of ≥90% for attaining an area under the curve (AUC)/MIC ratio of >25 with a standard dosage of doxycycline (5 mg/kg of body weight every 12 h) for strains with MICs of ≤0.125 μg/ml. Tetracycline predicted doxycycline susceptibility, but current tetracycline breakpoints were inappropriate for the interpretation of doxycycline susceptibility results. Accordingly, canine-specific doxycycline MIC breakpoints (susceptible, ≤0.125 μg/ml; intermediate, 0.25 μg/ml; resistant, ≥0.5 μg/ml) and zone diameter breakpoints (susceptible, ≥25 mm; intermediate, 21 to 24 mm; resistant, ≤20 mm) and surrogate tetracycline MIC breakpoints (susceptible, ≤0.25 μg/ml; intermediate, 0.5 μg/ml; resistant, ≥1 μg/ml) and zone diameter breakpoints (susceptible, ≥23 mm; intermediate, 18 to 22 mm; resistant, ≤17 mm) were proposed based on the data generated in this study.
          }, number={11}, journal={JOURNAL OF CLINICAL MICROBIOLOGY}, author={Maaland, Marit Gaastra and Papich, Mark G. and Turnidge, John and Guardabassi, Luca}, year={2013}, month={Nov}, pages={3547–3554} }
 @article{puza_papich_reinero_chang_yu_sharp_declue_2014, title={Pharmacokinetics and preliminary safety data of a single oral dose of bosentan, a dual endothelin receptor antagonist, in cats}, volume={37}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12083}, abstractNote={The objective of this study was to evaluate the pharmacokinetic properties and adverse effect profile of single‐dose oral bosentan, a dual endothelin receptor antagonist, in healthy cats. Pharmacokinetic parameters were determined following a single mean ± SD oral dose of 3.2 ± 0.6 mg/kg of bosentan in 6 adult cats. Blood was collected for quantification of bosentan via high‐performance liquid chromatography with ultraviolet detection. Blood and urine were evaluated for CBC, plasma biochemical profile, and urinalysis, and repeat physical examinations were performed to evaluate for adverse effects. The mean terminal half‐life of bosentan was 20.4 ± 17.2 h. The mean peak plasma concentration was 0.49 ± 0.24 g/mL, and the mean time to maximum plasma concentration was 6.8 ± 8.6 h. The area under the curve was 5.14 ± 3.81 h·μg/mL. Oral bosentan tablets were absorbed in cats, and no clinically important adverse events were noted. Further evaluation of repeat dosing, investigation into the in vivo efficacy of decreasing endothelin‐1 concentrations in cats, as well as safety in conjunction with other medications is warranted.}, number={2}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Puza, N. and Papich, M. G. and Reinero, C. and Chang, C. -H. and Yu, D. -H. and Sharp, C. and DeClue, A.}, year={2014}, month={Apr}, pages={192–195} }
 @article{maher_schnabel_cross_papich_divers_fortier_2014, title={Plasma and synovial fluid concentration of doxycycline following low-dose, low-frequency administration, and resultant inhibition of matrix metalloproteinase-13 from interleukin-stimulated equine synoviocytes}, volume={46}, ISSN={["2042-3306"]}, DOI={10.1111/evj.12139}, abstractNote={SummaryReasons for studyTo determine whether low‐dose, low‐frequency doxycycline administration is capable of achieving chondroprotective concentrations within synovial fluid (SF) while remaining below minimum inhibitory concentration 90 (MIC90) of most equine pathogens and would be an option in the management of osteoarthritis.ObjectivesTo determine whether low‐dose, low‐frequency oral administration of doxycycline can attain in vivo SF concentrations capable of chondroprotective effects through reduction of matrix metalloproteinase (MMP)‐13 activity, while remaining below MIC90 of most equine pathogens.Study designDescriptive pharmacokinetic study with crossover design.MethodsTwo groups of 6 horses received oral doxycycline. Plasma and SF doxycycline concentrations were measured using high performance liquid chromatography. Group 1 received 5 mg/kg bwt q. 24 h with 21 blood and 8 SF samples collected over 120 h; Group 2 received 5 mg/kg bwt q. 48 h with 27 blood and 11 SF samples collected over 192 h. Cultured synoviocytes were treated with interleukin‐1α (1 ng/ml) for 24 h to stimulate MMP synthesis, and then SF was added to the culture medium for 96 h. MMP‐13 protein and mRNA were measured in synoviocyte culture medium and synoviocytes, respectively.ResultsMean doxycycline concentration ≥0.043 μg/ml (previously demonstrated to inhibit MMP‐13) was achieved in plasma by t = 0.25 h and SF by t = 48 h in Group 1, and in plasma by t = 0.17 h and SF by t = 1 h in Group 2. Synoviocyte culture medium containing doxycycline from Groups 1 and 2 had significantly decreased active MMP‐13 protein concentration, and synoviocytes cultured in this medium had significantly decreased MMP‐13 gene expression compared to controls. Plasma doxycycline concentration in both groups and SF doxycycline concentration in Group 2 demonstrated a cumulative effect.ConclusionsLow‐dose orally administered doxycycline achieves SF concentrations in vivo capable of diminishing MMP‐13 expression. This study supports the use of doxycycline as a disease modifying osteoarthritic drug.}, number={2}, journal={EQUINE VETERINARY JOURNAL}, author={Maher, M. C. and Schnabel, L. V. and Cross, J. A. and Papich, M. G. and Divers, T. J. and Fortier, L. A.}, year={2014}, month={Mar}, pages={198–202} }
 @inbook{sykes_papich_2014, title={Principles of Antiinfective Therapy}, ISBN={9781437707953}, url={http://dx.doi.org/10.1016/b978-1-4377-0795-3.00006-5}, DOI={10.1016/b978-1-4377-0795-3.00006-5}, booktitle={Canine and Feline Infectious Diseases}, publisher={Elsevier}, author={Sykes, Jane E. and Papich, Mark G.}, year={2014}, pages={46–53} }
 @article{petritz_guzman_wiebe_papich_2013, title={Stability of three commonly compounded extemporaneous enrofloxacin suspensions for oral administration to exotic animals}, volume={243}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.243.1.85}, DOI={10.2460/javma.243.1.85}, abstractNote={Abstract
Objective—To evaluate the stability of 3 extemporaneous oral suspensions of enrofloxacin mixed with readily available flavoring vehicles when stored at room temperature (approx 22°C).
Design—Evaluation study.
Samples—3 commonly compounded oral suspensions of enrofloxacin.
Procedures—On day 0, commercially available enrofloxacin tablets were compounded with a mixture of distilled water and corn syrup (formulation A) or cherry syrup (formulation B) flavoring vehicles to create suspensions with a nominal enrofloxacin concentration of 22.95 mg/mL, and 2.27% enrofloxacin injectable solution was compounded with a liquid sweetener (formulation C) to create a suspension with a nominal enrofloxacin concentration of 11.35 mg/mL. Preparations were stored in amber-colored vials at room temperature for 56 days. For each preparation, the enrofloxacin concentration was evaluated with high-performance liquid chromatography at prespecified intervals during the study. The pH, odor, and consistency for all suspensions were recorded at the start and completion of the study.
Results—Relative to the nominal enrofloxacin concentration, the enrofloxacin concentration strength ranged from 95.80% to 100.69% for formulation A, 108.44% to 111.06% for formulation B, and 100.99% to 103.28% for formulation C. A mild pH increase was detected in all 3 suspensions during the study.
Conclusions and Clinical Relevance—Results indicated that, when stored in amber-colored vials at room temperature for 56 days, the enrofloxacin concentration strength in all 3 formulations was retained within acceptance criteria of 90% to 110%. Subjectively, cherry syrup flavoring was better at masking the smell and taste of enrofloxacin than were the other mixing vehicles.}, number={1}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Petritz, Olivia A. and Guzman, David Sanchez-Migallon and Wiebe, Valerie J. and Papich, Mark G.}, year={2013}, month={Jul}, pages={85–90} }
 @article{hopfensperger_messenger_papich_sherman_2013, title={The use of oral transmucosal detomidine hydrochloride gel to facilitate handling in dogs}, volume={8}, ISSN={["1878-7517"]}, DOI={10.1016/j.jveb.2012.10.004}, abstractNote={Safe and humane handling in the veterinary clinic can be challenging when dealing with fearful or anxious dogs. Historically, alpha-2 adrenergic agonists have been used via parenteral routes to facilitate handling of difficult canine subjects. Detomidine hydrochloride is an alpha-2 agonist sedative commercially available in an oral transmucosal (OTM) formulation (Dormosedan Gel; Pfizer Animal Health, Madison, NJ) approved for sedation and restraint in horses. The usefulness of this detomidine formulation has not been previously reported in dogs. This study evaluated the behavioral and physiological effects of OTM detomidine gel administration in dogs to assess its efficacy and safety for facilitation of handling canine subjects. Six healthy institution-owned adult dogs were administered detomidine gel at a dose of 0.35 mg/m2 via OTM route. Behavioral and physiological assessments were performed pretreatment and repeated every 15–30 minutes for 5 hours after administration. Behavioral assessments included global sedation (GS), composite sedation (CS), global anxiolysis (GA), and ease of handling (EH) scores. Physiological assessments included heart rate and rhythm, respiratory rate, mucous membrane color, indirect blood pressure, rectal temperature, oxygen saturation, and capillary refill time. Posttreatment GS, CS, GA, and EH scores were improved for all 6 subjects as compared with pretreatment. For 4 of 6 dogs, maximal GS scores occurred at 45 minutes posttreatment, and duration of maximal GS scores was 30 minutes. Five of 6 dogs achieved adequate GS scores. EH scores were significantly higher during time points of adequate GS scores as compared with time points when adequate GS scores were not achieved. The physiological measures revealed transient bradycardia in 5 of 6 dogs and intermittent second-degree atrioventricular block in 1 dog. No other significant adverse events were noted, and all dogs recovered uneventfully. OTM detomidine gel was safely administered to 6 dogs at a dose of 0.35 mg/m2 and resulted in measurable sedation, anxiolysis, and improved EH in all subjects. Although further evaluation is warranted for use in client-owned dogs, OTM detomidine gel offers a novel sedative and anxiolytic option to facilitate handling of canine subjects.}, number={3}, journal={JOURNAL OF VETERINARY BEHAVIOR-CLINICAL APPLICATIONS AND RESEARCH}, author={Hopfensperger, Marie J. and Messenger, Kristen M. and Papich, Mark G. and Sherman, Barbara L.}, year={2013}, pages={114–123} }
 @article{felt_papich_howard_long_mckeon_torreilles_green_2013, title={Tissue distribution of enrofloxacin in African clawed frogs (Xenopus laevis) after intramuscular and subcutaneous administration}, volume={52}, number={2}, journal={Journal of the American Association for Laboratory Animal Science}, author={Felt, S. and Papich, M. G. and Howard, A. and Long, T. and McKeon, G. and Torreilles, S. and Green, S.}, year={2013}, pages={186–188} }
 @article{levine_gookin_papich_davidson_2013, title={Twice-daily dosing of RDZ no longer recommended for treatment of intestinal Tritrichomonas foetus infection}, volume={16}, ISSN={1098-612X 1532-2750}, url={http://dx.doi.org/10.1177/1098612x13506430}, DOI={10.1177/1098612x13506430}, abstractNote={We would like to thank Xenoulis et al1 for their recent retrospective study in which information is provided on the outcome of cats that were treated with ronidazole for Tritrichomonas foetus infection. We agree with the authors’ recommendation of a treatment regimen for infections caused by T foetus of 30 mg/kg ronidazole (RDZ) q24h for 14 days.1 However, they reference a previous study of ours that recommended that cats that relapse should be treated with 30–50 mg/kg RDZ PO q12h.1,2 Based on our recent feline RDZ pharmacokinetic (PK) studies, we no longer recommend twice-daily dosing of RDZ.3 In our PK study, we determined that the half-life of RDZ is long (10.5 h), and that 48 h after a single dose of 30 mg/kg immediaterelease RDZ capsules orally there was still drug remaining in the cats’ plasma.3 Simulations based on our PK studies showed that twice-daily administration of 30 mg/kg RDZ PO would lead to drug accumulation.3 Neurotoxicity, including tremors, ataxia and agitation, is a reported and potentially dangerous side effect of RDZ in cats.4,5 As such, we no longer advocate twice-daily RDZ at this dose. However, it should also be noted that our PK studies did not assess the efficacy of our revised recommendations of once-daily 30 mg/kg RDZ administration for T foetus-infected cats. Such work remains to be done. We wanted to draw readers’ attention to these recent PK studies, so that cats are not inadvertently overdosed and risk neurologic sequelae based on outdated recommendations. References 1 Xenoulis PG, Lopinski DJ, Read SA, et al. Intestinal Tritrichomonas foetus infection in cats: a retrospective study of 104 cases. J Feline Med Surg 2013; 15: 1098–1103. 2 Gookin JL, Copple CN, Papich MG, et al. Efficacy of ronidazole for treatment of feline Tritrichomonas foetus infection. J Vet Intern Med 2006; 20: 536–543. 3 LeVine DN, Papich MG, Gookin JL, et al. Ronidazole pharmacokinetics after intravenous and oral immediaterelease capsule administration in healthy cats. J Feline Med Surg 2011; 13: 244–250. 4 Rosado TW, Specht A and Marks SL. Neurotoxicosis in four cats receiving ronidazole. J Vet Intern Med 2007; 21: 328–331. 5 Pham D. Chronic intermittent diarrhea in a 14-month-old Abyssinian cat. Can Vet J 2009; 50: 85–87.}, number={2}, journal={Journal of Feline Medicine and Surgery}, publisher={SAGE Publications}, author={LeVine, Dana N and Gookin, Jody L and Papich, Mark G and Davidson, Gigi S}, year={2013}, month={Oct}, pages={198–198} }
 @article{papich_2012, title={Ciprofloxacin pharmacokinetics and oral absorption of generic ciprofloxacin tablets in dogs}, volume={73}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.73.7.1085}, abstractNote={Abstract
Objective—To determine the pharmacokinetics of ciprofloxacin in dogs, including oral absorption following administration of generic ciprofloxacin tablets.
Animals—6 healthy Beagles.
Procedures—In a crossover study design, ciprofloxacin was administered as a generic tablet (250 mg, PO; mean dose, 23 mg/kg) and solution (10 mg/kg, IV) to 6 dogs. In a separate experiment, 4 of the dogs received ciprofloxacin solution (10 mg/mL) PO via stomach tube (total dose, 250 mg). Blood samples were collected before (time 0) and for 24 hours after each dose. Plasma concentrations were analyzed with high-pressure liquid chromatography. Pharmacokinetic analysis was performed by means of compartmental modeling.
Results—When ciprofloxacin was administered as tablets PO, peak plasma concentration was 4.4 μg/mL (coefficient of variation [CV], 55.9%), terminal half-life (t1/2) was 2.6 hours (CV, 10.8%), area under the time-concentration curve was 22.5 μg•h/mL (CV, 62.3%), and systemic absorption was 58.4% (CV, 45.4%). For the dose administered IV, t1/2 was 3.7 hours (CV, 52.3%), clearance was 0.588 L/kg/h (CV, 33.9%), and volume of distribution was 2.39 L/kg (CV, 23.7%). After PO administration as a solution versus IV administration, plasma concentrations were more uniform and consistent among dogs, with absorption of 71% (CV, 7.3%), t1/2 of 3.1 hours (CV, 18.6%), and peak plasma concentration of 4.67 μg/mL (CV, 17.6%).
Conclusions and Clinical Relevance—Inconsistent oral absorption of ciprofloxacin in some dogs may be formulation dependent and affected by tablet dissolution in the small intestine. Because of the wide range in oral absorption of tablets, the dose needed to reach the pharmacokinetic-pharmacodynamic target concentration in this study ranged from 12 to 52 mg/kg (CV, 102%), with a mean dose of 25 mg/kg, once daily, for bacteria with a minimum inhibitory concentration ≤ 0.25 μg/mL.}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Papich, Mark G.}, year={2012}, month={Jul}, pages={1085–1091} }
 @misc{martinez_papich_drusano_2012, title={Dosing Regimen Matters: the Importance of Early Intervention and Rapid Attainment of the Pharmacokinetic/Pharmacodynamic Target}, volume={56}, ISSN={["0066-4804"]}, DOI={10.1128/aac.05360-11}, abstractNote={ABSTRACT
          To date, the majority of pharmacokinetic/pharmacodynamic (PK/PD) discussions have focused on PK/PD relationships evaluated at steady-state drug concentrations. However, a concern with reliance upon steady-state drug concentrations is that it ignores events occurring while the pathogen is exposed to intermittent suboptimal systemic drug concentrations prior to the attainment of a steady state. Suboptimal (inadequate) exposure can produce amplification of resistant bacteria. This minireview provides an overview of published evidence supporting the positions that, in most situations, it is the exposure achieved during the first dose that is relevant for determining the therapeutic outcome of an infection, therapeutic intervention should be initiated as soon as possible to minimize the size of the bacterial burden at the infection site, and the duration of drug administration should be kept as brief as clinically appropriate to reduce the risk of selecting for resistant (or phenotypically nonresponsive) microbial strains. To support these recommendations, we briefly discuss data on inoculum effects, persister cells, and the concept of time within some defined mutation selection window.}, number={6}, journal={ANTIMICROBIAL AGENTS AND CHEMOTHERAPY}, author={Martinez, Marilyn N. and Papich, Mark G. and Drusano, George L.}, year={2012}, month={Jun}, pages={2795–2805} }
 @article{martinez_papich_2012, title={Drug solubility classification in the dog}, volume={35}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2012.01373.x}, abstractNote={Martinez, M. N., Papich, M. G. Drug solubility classification in the dog. J. vet. Pharmacol. Therap. 35 (Suppl. 1), 87–91.Similar to human drugs, oral drug delivery is a major route of drug administration in dogs. Therefore, it is important to consider how the physiological characteristics of the dog may influence the considerations that go into the classification of drug solubility. In this manuscript, we discuss the impact of body size vs. administered dose and gastric volume on the estimated gastric drug concentration that needs to be considered. However, when using a dose number (Do) paradigm, there are very few drugs for which the different methods of estimating gastric volume will alter the drug solubility classification. We also evaluate the range of pH values under which a solubility assessment should be generated and conclude that despite specific differences in the pH values of the gastrointestinal environment of people and dogs, the human pH criteria for evaluating drug solubility can be used when evaluating drug solubility of oral medications in dogs.}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Martinez, M. N. and Papich, M. G.}, year={2012}, month={Apr}, pages={87–91} }
 @article{hart_barrett_brown_papich_powers_sullins_2013, title={Elution of antimicrobials from a cross-linked dextran gel: In vivo Quantification}, volume={45}, ISSN={["2042-3306"]}, DOI={10.1111/j.2042-3306.2012.00633.x}, abstractNote={SummaryReasons for performing study: Use of a novel, biodegradable, antimicrobial‐impregnated gel provides an alternative method of local treatment of infections in horses.Objectives: To determine in vivo elution of antimicrobial medications from antimicrobial‐impregnated cross‐linked dextran gel and to evaluate the effect on wound healing when implanted subcutaneously in horses.Methods: Amikacin‐, vancomycin‐ or amikacin/clindamycin‐impregnated gel was placed subcutaneously in 11 horses' necks, using 6 replicates with a 3 month washout between experiments. Capillary ultrafiltration probes for collection of interstitial fluid were placed 0 cm and 1.5 cm from the gel‐filled incisions. Samples were collected at 0, 4, 8 and 12 h, and on Days 1–10. Blood was collected on Days 0, 1 and 7. Amikacin and vancomycin samples were analysed via fluorescence polarisation immunoassay, and clindamycin samples via high‐performance liquid chromatography. Histology of biopsy samples was performed at the completion of the study. Differences in mean histomorphological scores between groups were assessed using Wilcoxon's signed ranks test.Results: Maximum antimicrobial concentrations were detected at 4 h (amikacin), and 8 h (vancomycin, and amikacin and clindamycin from the combination gel). Mean ± s.d. peak concentrations for amikacin, vancomycin, amikacin (amikacin/clindamycin) and clindamycin were 6133 ± 1461, 7286 ± 2769, 3948 ± 317 and 985 ± 960, respectively. Median number of days for which antimicrobial concentration remained above minimum inhibitory concentration for target microorganisms at implantation was ≥10 days for vancomycin, 9 days (± 1) for amikacin and 8 days (± 1) for clindamycin. Mean plasma amikacin and vancomycin concentrations were lower than detectable limits; mean serum clindamycin concentrations were 0.52 µg/ml and 0.63 µg/ml at 24 h and 7 days, respectively. There were no significant differences in histomorphological scores between treatment and control incisions (P≥0.22).Conclusions and potential relevance: Cross‐linked dextran gel is a safe, effective alternative local antimicrobial delivery method.}, number={2}, journal={EQUINE VETERINARY JOURNAL}, author={Hart, S. K. and Barrett, J. G. and Brown, J. A. and Papich, M. G. and Powers, B. E. and Sullins, K. E.}, year={2013}, month={Mar}, pages={148–153} }
 @article{papich_levine_gookin_davidson_stagner_hayes_2013, title={Ronidazole pharmacokinetics in cats following delivery of a delayed-release guar gum formulation}, volume={36}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12019}, abstractNote={Ronidazole (RDZ) is the only known effective treatment for feline diarrhea caused by Tritrichomonas foetus. This study aimed to develop guar gum‐coated colon‐targeted tablets of RDZ and to determine the pharmacokinetics of this delayed‐release formulation in cats. Guar gum‐coated tablets were administered orally once to five healthy cats (mean dose 32.3 mg/kg). The tablets were then administered once daily for 5 days to four cats (mean dose 34.5 mg/kg), and absorption studies repeated on day 5. Plasma was collected and analyzed for RDZ concentration, and pharmacokinetic noncompartmental and deconvolution analysis were performed on the data. There was negligible RDZ release until after 6 h, and a delayed peak plasma concentration (mean Cmax 28.9 μg/mL) at approximately 14.5 h, which coincides with colonic arrival in cats. Maximum input rate (mg/kg per hour) occurred between 6 and 16 h. This delayed release of ronidazole from guar gum‐coated tablets indicates that release of RDZ may be delayed to deliver the medication to a targeted area of the intestine. Repeated dosing with guar gum tablets to steady‐state did not inhibit drug bioavailability or alter the pharmacokinetics. Such targeted RDZ drug delivery may provide improved efficacy and reduce adverse effects in cats.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Papich, M. G. and LeVine, D. N. and Gookin, J. L. and Davidson, G. S. and Stagner, W. C. and Hayes, R. B.}, year={2013}, month={Aug}, pages={399–407} }
 @article{papich_2012, title={Selection of antibiotics for meticillin-resistant Staphylococcus pseudintermedius: time to revisit some old drugs?}, volume={23}, ISSN={["1365-3164"]}, DOI={10.1111/j.1365-3164.2011.01030.x}, abstractNote={The aim of this review is to consider systemic therapy options for meticillin‐resistantStaphylococcus pseudintermedius(MRSP).Infections caused by MRSP in small animals – particularly dogs – have been frustrating veterinarians in recent years. After a susceptibility test is performed, veterinarians are left to select from drugs that have not been frequently encountered on a susceptibility report. Some of these are old drugs that have not been used regularly by veterinary dermatologists.As MRSP is, by definition, resistant to all β‐lactam antibiotics, including cephalosporins, penicillins and amoxicillin–clavulanate combinations, the β‐lactam drugs are not an option for systemic treatment. As most MRSPs are multidrug resistant, familiar drugs, such as trimethoprim–sulfonamides, fluoroquinolones, macrolides and lincosamides (clindamycin), are also not usually an option for treatment.Therefore, veterinarians are left with drugs such as rifampicin, chloramphenicol, tetracyclines, aminoglycosides and vancomycin to choose from on the basis of anin vitrosusceptibility test. Some of these drugs were originally approved over 50 years ago and may not be familiar to some veterinarians. Each of these drugs possesses unique properties and has particular advantages and disadvantages. Veterinarians should be particularly aware of the adverse effects, limitations and precautions when using these drugs.New drugs also have been developed for meticillin‐resistantStaphylococcus aureusin humans. These include linezolid, ceftaroline, daptomycin and tigecycline. Although these drugs are very infrequently – if ever – considered for veterinary use, the properties of these drugs should also be known to veterinary dermatologists.}, number={4}, journal={Veterinary Dermatology}, author={Papich, M.G.}, year={2012}, month={Aug}, pages={352–60} }
 @inbook{apley_crist_gonzalez_hunter_martinez_modric_papich_parr_riviere_marques_2012, title={Solubility criteria for veterinary drugs}, url={http://www.usp.org/sites/default/files/usp_pdf/en/s200600.pdf}, booktitle={Stimuli Article}, publisher={United States Pharmacopeia, Pharmacopeial Forum (PF)}, author={Apley, M. and Crist, B. and Gonzalez, M.A. and Hunter, R.P. and Martinez, M.N. and Modric, S. and Papich, M.G. and Parr, A.F. and Riviere, J.E. and Marques, M.R.C.}, year={2012} }
 @article{crook_early_messenger_munana_gallagher_papich_2013, title={The pharmacokinetics of cytarabine in dogs when administered via subcutaneous and continuous intravenous infusion routes}, volume={36}, ISSN={["1365-2885"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84880035701&partnerID=MN8TOARS}, DOI={10.1111/jvp.12008}, abstractNote={This crossover study compared the pharmacokinetics of cytarabine in six healthy dogs following intravenous constant rate infusion (CRI) and subcutaneous (SC) administrations, as these are two routes of administration commonly employed in the treatment of meningoencephalitis of unknown etiology. Each dog received a SC cytarabine injection of 50 mg/m2 or an 8 h CRI of 25 mg/m2 per hour, with a 7‐day washout before receiving the alternative treatment. Blood samples were collected for 16 h after CRI initiation and for 8 h after SC injection. Plasma concentrations were measured by high‐pressure liquid chromatography (HPLC). Pharmacokinetic parameters were estimated using the best‐fit compartmental analysis for both CRI and SC routes. Terminal half‐life (T½) of cytarabine was 1.35 ± 0.3 and 1.15 ± 0.13 h after SC administration and CRI, respectively. Mean peak concentration (Cmax) was 2.88 and 2.80 μg/mL for SC and CRI administration, respectively. Volume of distribution was 0.66 ± 0.07 l/kg. The 8‐h CRI produced steady‐state plasma concentrations as determined by consecutive measurement that did not decline until the end of the infusion. The SC administration did not achieve steady‐state concentrations because cytarabine administered by this route was rapidly absorbed and eliminated quickly. The steady state achieved with the cytarabine CRI may produce a more prolonged exposure of cytarabine at cytotoxic levels in plasma compared to the concentrations after SC administration.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Crook, K. I. and Early, P. J. and Messenger, K. M. and Munana, K. R. and Gallagher, R. and Papich, M. G.}, year={2013}, month={Aug}, pages={408–411} }
 @article{schwartz_munana_nettifee-osborne_messenger_papich_2013, title={The pharmacokinetics of midazolam after intravenous, intramuscular, and rectal administration in healthy dogs}, volume={36}, ISSN={["0140-7783"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84883647308&partnerID=MN8TOARS}, DOI={10.1111/jvp.12032}, abstractNote={Intravenous benzodiazepines are utilized as first‐line drugs to treat prolonged epileptic seizures in dogs and alternative routes of administration are required when venous access is limited. This study compared the pharmacokinetics of midazolam after intravenous (IV), intramuscular (IM), and rectal (PR) administration. Six healthy dogs were administered 0.2 mg/kg midazolam IV, IM, or PR in a randomized, 3‐way crossover design with a 3‐day washout between study periods. Blood samples were collected at baseline and at predetermined intervals until 480 min after administration. Plasma midazolam concentrations were measured by high‐pressure liquid chromatography with UV detection. Rectal administration resulted in erratic systemic availability with undetectable to low plasma concentrations. Arithmetic mean values ± SD for midazolam peak plasma concentrations were 0.86 ± 0.36 μg/mL (C0) and 0.20 ± 0.06 μg/mL (Cmax), following IV and IM administration, respectively. Time to peak concentration (Tmax) after IM administration was 7.8 ± 2.4 min with a bioavailability of 50 ± 16%. Findings suggest that IM midazolam might be useful in treating seizures in dogs when venous access is unavailable, but higher doses may be needed to account for intermediate bioavailability. Rectal administration is likely of limited efficacy for treating seizures in dogs.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Schwartz, M. and Munana, K. R. and Nettifee-Osborne, J. A. and Messenger, K. M. and Papich, M. G.}, year={2013}, month={Oct}, pages={471–477} }
 @article{weese_blondeau_boothe_breitschwerdt_guardabassi_hillier_lloyd_papich_rankin_turnidge_et al._2011, title={Antimicrobial use guidelines for treatment of urinary tract disease in dogs and cats: antimicrobial guidelines working group of the international society for companion animal infectious diseases}, volume={2011}, ISSN={2042-0048}, url={http://dx.doi.org/10.4061/2011/263768}, DOI={10.4061/2011/263768}, abstractNote={Urinary tract disease is a common reason for use (and likely misuse, improper use, and overuse) of antimicrobials in dogs and cats. There is a lack of comprehensive treatment guidelines such as those that are available for human medicine. Accordingly, guidelines for diagnosis and management of urinary tract infections were created by a Working Group of the International Society for Companion Animal Infectious Diseases. While objective data are currently limited, these guidelines provide information to assist in the diagnosis and management of upper and lower urinary tract infections in dogs and cats.}, journal={Veterinary Medicine International Epub}, publisher={Hindawi Limited}, author={Weese, J.S. and Blondeau, J.M. and Boothe, D. and Breitschwerdt, E.B. and Guardabassi, L. and Hillier, A. and Lloyd, D.H. and Papich, M.G. and Rankin, S.C. and Turnidge, J.D. and et al.}, year={2011}, month={Jun}, pages={1–9} }
 @article{messenger_papich_blikslager_2011, title={Distribution of enrofloxacin and its active metabolite, using an in vivo ultrafiltration sampling technique after the injection of enrofloxacin to pigs}, volume={35}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/j.1365-2885.2011.01338.x}, DOI={10.1111/j.1365-2885.2011.01338.x}, abstractNote={Messenger, K. M., Papich, M. G., Blikslager, A. T. Distribution of enrofloxacin and its active metabolite, using anin vivoultrafiltration sampling technique after the injection of enrofloxacin to pigs.J. vet. Pharmacol. Therap. 35, 452–459.The objective of this study was to determine the pharmacokinetics (PK) of enrofloxacin in pigs and compare to the tissue interstitial fluid (ISF). Six healthy, young pigs were administered 7.5 mg/kg enrofloxacin subcutaneously (SC). Blood and ISF samples were collected from preplaced intravenous catheters and ultrafiltration sampling probes placed in three different tissue sites (intramuscular, subcutaneous, and intrapleural). Enrofloxacin concentrations were measured using high‐pressure liquid chromatography with fluorescence detection, PK parameters were analyzed using a one‐compartment model, and protein binding was determined using a microcentrifugation system. Concentrations of the active metabolite ciprofloxacin were negligible. The mean ± SD enrofloxacin plasma half‐life, volume of distribution, clearance, and peak concentration were 26.6 ± 6.2 h (harmonic mean), 6.4 ± 1.2 L/kg, 0.18 ± 0.08 L/kg/h, and 1.1 ± 0.3 μg/mL, respectively. The half‐life of enrofloxacin from the tissues was 23.6 h, and the maximum concentration was 1.26 μg/mL. Tissue penetration, as measured by a ratio of area‐under‐the‐curve (AUC), was 139% (±69%). Plasma protein binding was 31.1% and 37.13% for high and low concentrations, respectively. This study demonstrated that the concentration of biologically active enrofloxacin in tissues exceeds the concentration predicted by the unbound fraction of enrofloxacin in pig plasma. At a dose of 7.5 mg/kg SC, the high tissue concentrations and long half‐life produce an AUC/MIC ratio sufficient for the pathogens that cause respiratory infections in pigs.}, number={5}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Messenger, K. M. and Papich, M. G. and Blikslager, A. T.}, year={2011}, month={Sep}, pages={452–459} }
 @article{messenger_papich_blikslager_2011, title={Distribution of enrofloxacin and its active metabolite, using an in vivo ultrafiltration sampling technique after the injection of enrofloxacin to pigs}, volume={9}, DOI={10.1111/j.1365-2885.2011.01338}, journal={Journal of Veterinary Pharmacology & Therapeutics}, author={Messenger, K.M. and Papich, M.G. and Blikslager, A.T.}, year={2011}, month={Sep} }
 @article{holmes_bedenice_papich_2012, title={Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and intramuscular injection}, volume={35}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2011.01323.x}, abstractNote={Holmes, K., Bedenice, D., Papich, M. G. Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and intramuscular injection.J. vet. Pharmacol. Therap. 35, 382–388.A single dose of florfenicol (Nuflor®) was administered to eight healthy adult alpacas at 20 mg/kg intramuscular (i.m.) and 40 mg/kg subcutaneous (s.c.) using a randomized, cross‐over design, and 28‐day washout period. Subsequently, 40 mg/kg florfenicol was injected s.c. every other day for 10 doses to evaluate long‐term effects. Maximum plasma florfenicol concentrations (Cmax, measured via high‐performance liquid chromatography) were achieved rapidly, leading to a higher Cmaxof 4.31 ± 3.03 μg/mL following administration of 20 mg/kg i.m. than 40 mg/kg s.c. (Cmax: 1.95 ± 0.94 μg/mL). Multiple s.c. dosing at 48 h intervals achieved a Cmaxof 4.48 ± 1.28 μg/mL at steady state. The area under the curve and terminal elimination half‐lives were 51.83 ± 11.72 μg/mL·h and 17.59 ± 11.69 h after single 20 mg/kg i.m. dose, as well as 99.78 ± 23.58 μg/mL·h and 99.67 ± 59.89 h following 40 mg/kg injection of florfenicol s.c., respectively. Florfenicol decreased the following hematological parameters after repeated administration between weeks 0 and 3: total protein (6.38 vs. 5.61 g/dL,P < 0.0001), globulin (2.76 vs. 2.16 g/dL,P < 0.0003), albumin (3.61 vs. 3.48 g/dL,P = 0.0038), white blood cell count (11.89 vs. 9.66 × 103/μL,P < 0.044), and hematocrit (27.25 vs. 24.88%,P < 0.0349). Significant clinical illness was observed in one alpaca. The lowest effective dose of florfenicol should thus be used in alpacas and limited to treatment of highly susceptible pathogens.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Holmes, K. and Bedenice, D. and Papich, M. G.}, year={2012}, month={Aug}, pages={382–388} }
 @article{holmes_bedenice_papich_2011, title={Florfenicol pharmacokinetics in healthy adult alpacas after subcutaneous and intramuscular injection}, volume={8}, DOI={10.1111/j.1365-2885.2011.01323}, journal={Journal of Veterinary Pharmacology & Therapeutics}, author={Holmes, K. and Bedenice, D. and Papich, M.G.}, year={2011}, month={Aug} }
 @book{papich_2011, place={St. Louis, Missouri}, title={Handbook of Antimicrobial Therapy for Small Animals}, publisher={Elsevier-Saunders}, author={Papich, M.G.}, year={2011} }
 @article{watts_nixon_papich_sparks_schwark_2011, title={In Vitro Elution of Amikacin and Ticarcillin from a Resorbable, Self-Setting, Fiber Reinforced Calcium Phosphate Cement}, volume={40}, ISSN={["1532-950X"]}, DOI={10.1111/j.1532-950x.2011.00831.x}, abstractNote={Objective:To determinein vitroelution characteristics of amikacin and ticarcillin from fiber reinforced calcium phosphate beads (FRCP).Sample Population:Experimental.Methods:FRCP beads with water (A), amikacin (B), ticarcillin/clavulanate (C), or both amikacin and ticarcillin/clavulanate (D) were bathed in mL phosphate‐buffered saline (PBS) at 37°C, 5% CO2and 95% room air. PBS was sampled (eluent) and beads were placed in fresh PBS at time points 1 and 8 hours and 1, 2, 3, 4, 5, 6, 7, 10, 12, 14, 18, 21, 25, 28, 35, 42, 49, and 56 days. Antibiotic concentration and antimicrobial activity of eluent againstEscherichia coli, Staphylococcus aureus, andKlebsiella pneumoniaewere determined.Results:Both antibiotics eluted in a bimodal pattern. Beads with a single antibiotic eluted 20.8 ± 2.5% of amikacin and 29.5 ± 0.8% of ticarcillin over 56 days. Coelution of the antibiotics resulted in a lower proportion (AUC0–∞) of antibiotics eluted for both amikacin (9.5 ± 0.2%) and ticarcillin (21.7 ± 0.09%). Bioassay of antimicrobial activity of the eluent (t=1, 8, and 24 hours) established reduced antimicrobial activity of amikacin from combination beads (D).Conclusions:FRCP beads with amikacin or ticarcillin/clavulanate, but not the combination, are suitable carriers for wound implantation.Clinical Relevance:Duration before complete resorption of FRCP beadsin vivoshould be determined before clinical use as a resorbable depot. The results of this study underscore the importance of testing drug combinations, despite success of the combination systemically, before their use in local applications.}, number={5}, journal={VETERINARY SURGERY}, author={Watts, Ashlee E. and Nixon, Alan J. and Papich, Mark G. and Sparks, Holly D. and Schwark, Wayne S.}, year={2011}, month={Jul}, pages={563–570} }
 @article{singer_cohn_reinero_papich_2011, title={Leflunomide pharmacokinetics after single oral administration to dogs}, volume={34}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2011.01275.x}, abstractNote={Dogs are susceptible to a variety of immune-mediated diseases usually treated with corticosteroids, but these drugs cause important morbidity (Elwood & Polton, 2008; Putsche & Kohn, 2008). Alternative and adjunctive immunosuppressive treatments like leflunomide have met anecdotal success. Labeled for treatment of rheumatoid arthritis in humans, it has been used to treat other immune-mediated diseases and to prevent renal transplant rejection (Nguyen et al., 2004; Leca, 2009). After oral administration, leflunomide is rapidly metabolized to the active metabolite A77-1726 (teriflunomide). Two mechanisms of action have been described for the active metabolite. An enzyme involved in pyrimidine synthesis (dihydroorotate dehydrogenase) is inhibited thereby arresting lymphocyte activation and expansion, and tyrosine kinases involved in cellular differentiation and signal transduction are inhibited (Bartlett et al., 1991; Cherwinski et al., 1995; Fox et al., 1999). Leflunomide has been used as an adjunctive therapy for dogs refractory to traditional immunosuppressive drugs and to prevent anti-allograft immune responses (Gregory et al., 1998a,b; Affolter & Moore, 2000; Bianco & Hardy, 2009; Colopy et al., 2010). While doses £ 4 mg ⁄ kg ⁄ day have been used in dogs with no reported adverse effects, anemia and anorexia have been observed at doses >4 mg ⁄ kg ⁄ day (McChesney et al., 1994). Pharmacokinetic studies reported in people show that the active metabolite A77-1726 has a very long half-life (7–10 days) (Li et al., 2002; Rozman, 2002). Little pharmacokinetic data have been published regarding this drug in dogs. (McChesney et al., 1994) Using a small population of animals available for study, our objective was to present additional preliminary data on the pharmacokinetics of leflunomide and its metabolite, teriflunomide, that can potentially serve as a basis for further study. Four female intact mongrel dogs between 6 and 17 months old and weighing between 16.7 and 18 kg (mean, 17.4 kg) were used. All dogs were judged to be in good health based on physical examination, complete blood count, serum biochemistry, and urinalysis. Dogs were cared for in accordance with the NIH Guide for the Care and Use of Laboratory Animals, and all procedures were approved by the Animal Care and Use Committee at the University of Missouri-Columbia. Dogs were monitored daily for appetite and attitude. Four additional untreated young adult healthy pet dogs belonging to the investigators were used to obtain small volumes of blood for use in drug protein binding studies. Each of four study dogs received 4 mg ⁄ kg leflunomide orally once. A combination of 10 mg (Apotex Inc., Toronto, Ontario) and 20 mg (Sandoz Inc., Princeton, New Jersey) tablets were placed in a small volume of canned food; dogs were watched to ensure that the food and tablets were consumed and that there was no regurgitation or vomiting. Jugular venous blood samples (8 mL) were collected at time 0, prior to administration of leflunomide, at 1, 2, 4, 8, 12, 24 h and at 2, 4, 6, 8, 10, 12, 14, 16, 17 days after oral leflunomide administration. Blood samples were immediately placed on ice in plastic tubes containing lithium heparin for a maximum of 15 min before processing. Samples were centrifuged at 1250 g for 10 min at 4 C, and plasma was collected and stored at )80 C until analysis. Canine plasma samples were analyzed for leflunomide and teriflunomide concentrations by HPLC using a modification of previously described methods (Chan et al., 2004; van Roon et al., 2005). The reference standard compounds were purchased from the drug manufacturer (Sanofi Aventis; Deutschland GmbH, Frankfurt, Germany) and were dissolved in methanol to make up a 1 mg ⁄ mL standard solution. Further dilutions were made in distilled water to use as fortifying solutions to generate calibration curves in plasma. The stock solution was kept at 4 C in a tightly sealed dark vial. Reference standard solutions were added to blank (control) plasma, to make up seven calibration standards (range 0.00 lg ⁄ mL to 10 lg ⁄ mL). The mobile phase for HPLC analysis consisted of acetonitrile (52%) and 0.1% trifluoroacetic acid (48%). The HPLC system consisted of a quaternary solvent delivery system at a flow rate of 1 mL ⁄ min, an autosampler, and UV detector set at a wavelength of 295 nm (Agilent Technologies, Wilmington, DE, USA). A C18 reverse-phase column (Agilent Technologies) was used for separation and kept at a constant temperature of 40 C. All incurred plasma samples, calibration samples, and blank (control) plasma samples were prepared identically. Solid phase extraction J. vet. Pharmacol. Therap. 34, 609–611. doi: 10.1111/j.1365-2885.2011.01275.x. SHORT COMMUNICATION}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Singer, L. M. and Cohn, L. A. and Reinero, C. R. and Papich, M. G.}, year={2011}, month={Dec}, pages={609–611} }
 @article{kukanich_papich_2011, title={Pharmacokinetics and antinociceptive effects of oral tramadol hydrochloride administration in Greyhounds}, volume={72}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.72.2.256}, abstractNote={AbstractObjective—To determine the pharmacokinetics of tramadol, the active metabolite O-desmethyltrcamadol, and the metabolites N-desmethyltramadol and N,O-didesmethyltramadol after oral tramadol administration and to determine the antinociceptive effects of the drug in Greyhounds.
Animals—6 healthy 2- to 3-year-old Greyhounds (3 male and 3 female), weighing 25.5 to 41.1 kg.
Procedures—A mean dose of 9.9 mg of tramadol HCl/kg was administered PO as whole tablets. Blood samples were obtained prior to and at various points after administration to measure plasma concentrations of tramadol and its metabolites via liquid chromatography with mass spectrometry. Antinociceptive effects were determined by measurement of pain-pressure thresholds with a von Frey device.
Results—Tramadol was well tolerated, and a significant increase in pain-pressure thresholds was evident 5 and 6 hours after administration. The mean maximum plasma concentrations of tramadol, O-desmethyltramadol, N-desmethyltramadol, and N,O-didesmethyltramadol were 215.7, 5.7, 379.1, and 2372 ng/mL, respectively. The mean area-under-the-curve values for the compounds were 592, 16, 1,536, and 1,013 h·ng/mL, respectively. The terminal half-lives of the compounds were 1.1, 1.4, 2.3, and 3.6 hours, respectively. Tramadol was detected in urine 5 days, but not 7 days, after administration.
Conclusions and Clinical Relevance—Oral tramadol administration yielded antinociceptive effects in Greyhounds, but plasma concentrations of tramadol and O-desmethyltramadol were lower than expected. Compared with the approved dose (100 mg, PO) in humans, a mean dose of 9.9 mg/kg, PO resulted in similar tramadol but lower O-desmethyltramadol plasma concentrations in Greyhounds.}, number={2}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={KuKanich, Butch and Papich, Mark G.}, year={2011}, month={Feb}, pages={256–262} }
 @article{schnabel_papich_divers_altier_aprea_mccarrel_fortier_2012, title={Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations}, volume={44}, ISSN={["0425-1644"]}, DOI={10.1111/j.2042-3306.2011.00459.x}, abstractNote={SummaryReasons for performing study: Minocycline holds great potential for use in horses not only for its antimicrobial effects but also for its anti‐inflammatory and neuroprotective properties. However, there are no pharmacokinetic or safety data available regarding the use of oral minocycline in horses.Objectives: To determine pharmacokinetics, safety and penetration into plasma, synovial fluid, aqueous humour (AH) and cerebral spinal fluid (CSF) of minocycline after oral administration of multiple doses in horses and to determine the minimum inhibitory concentrations (MIC) of minocycline for equine pathogenic bacteria.Methods: Six horses received minocycline (4 mg/kg bwt q. 12 h for 5 doses). Thirty‐three blood and 9 synovial fluid samples were collected over 96 h. Aqueous humour and CSF samples were collected 1 h after the final dose. Minocycline concentrations were measured using high pressure liquid chromatography. The MIC values of minocycline for equine bacterial isolates were determined.Results: At steady state, the mean ± s.d. peak concentration of minocycline in the plasma was 0.67 ± 0.26 µg/ml and the mean half‐life was 11.48 ± 3.23 h. The highest trough synovial fluid minocycline concentration was 0.33 ± 0.12 µg/ml. The AH concentration of minocycline was 0.09 ± 0.03 µg/ml in normal eyes and 0.11 ± 0.04 µg/ml in blood aqueous barrier‐disrupted eyes. The mean CSF concentration of minocycline was 0.38 ± 0.09 µg/ml. The MIC values were determined for 301 isolates. Minocycline concentrations were above the MIC50 and MIC90 for many gram‐positive equine pathogens.Potential relevance: This study supports the use of orally administered minocycline at a dose of 4 mg/kg bwt every 12 h for the treatment of nonocular infections caused by susceptible (MIC≤0.25 µg/ml) organisms in horses. Further studies are required to determine the dose that would be effective for the treatment of ocular infections.}, number={4}, journal={EQUINE VETERINARY JOURNAL}, author={Schnabel, L. V. and Papich, M. G. and Divers, T. J. and Altier, C. and Aprea, M. S. and McCarrel, T. M. and Fortier, L. A.}, year={2012}, month={Jul}, pages={453–458} }
 @article{schnabel_papich_divers_altier_aprea_mccarrel_fortier_2011, title={Pharmacokinetics and distribution of minocycline in mature horses after oral administration of multiple doses and comparison with minimum inhibitory concentrations}, volume={9}, DOI={10.1111/j.2042-3306.2011.00459}, journal={Equine Veterinary Journal}, author={Schnabel, L.V. and Papich, M.G. and Divers, T.J. and Altier, C. and Aprea, M.S. and McCarrel, T.M. and Fortier, L.A.}, year={2011}, month={Sep} }
 @article{lewis_cohn_birkenheuer_papich_2012, title={Pharmacokinetics of diminazene diaceturate in healthy cats}, volume={35}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2011.01359.x}, abstractNote={Survival of five of six cats treated for acute cytauxzoonosis with diminazene aceturate has been reported (Greene et al., 1999). Diminazene, an aromatic diamidine, has been used to treat babesiosis and trypanosomiasis in dogs, leishmaniasis in humans, and a variety of other protozoal diseases in domestic livestock. It was administered at a dose of 2 mg ⁄ kg IM (two doses, 1 week apart) in the few cats with C. felis infection. Diminazene was administered to seven cats experimentally infected with Trypanosoma evansi at a dose of 3.5 mg ⁄ kg via intramuscular injection on five consecutive days (DaSilva et al., 2009). The treatment was 85.7% efficacious in eliminating the parasite, and no adverse effects were observed. Although commercially available in both aceturate (MW 515.5) and diaceturate (MW 587.6) salts, the drug is not Food and Drug Administration approved for use in any species in the United States of America. Feline cytauxzoonosis is a disease with high morbidity and mortality. Left untreated, 97% of cats with clinical cytauxzoonosis will die of the disease (Birkenheuer et al., 2006). Recently, the combination of the anti-malarial drug atovaquone with the antibiotic imidocarb dipropionate produced improved survival, but 40% of treated cats still died of the disease (Cohn et al., 2011). Additionally, this combination therapy requires thrice-daily oral dosing and can be prohibitively expensive. Diminazene, if found to be effective for the treatment of C. felis, would offer advantages both in practicality of dosing and in cost. Before additional clinical studies can be performed, the disposition of diminazene needs investigation. Therefore, our study objective was to characterize the pharmacokinetic profile of diminazene diaceturate in cats. Four adult cats (two male and two female) weighing 3.1– 5.3 kg were used. The cats were healthy based on physical examination, CBC, biochemical panel, and urinalysis. The day prior to study, cats were sedated with propofol (3–5 mg ⁄ kg to effect), and indwelling jugular catheters were placed to facilitate sample collection for the first 48 h. After that, samples were collected via jugular or medial saphenous venipuncture. Heparinized blood samples (2.0 mL) were collected just before (hour 0) and 0.5, 1, 2, 4, 8, 12, 18, 24, 36, 48, 72, 120, and 168 hours after intramuscular administration of diminazene diaceturate. Plasma was separated by centrifugation within 30 min of collection and frozen ()80 C) until analysis. Cats were observed several times daily to monitor for adverse events such as anorexia, lethargy, injection site pain, abnormal mentation, seizures, vomiting, ptylism, or diarrhea. Temperature, heart rate, respiratory rate, and effort were recorded 0, 12, 24, 48, 72, 120, and 168 h after drug administration. At 168 h after injection, CBC, biochemical panel, and urinalysis were repeated. All procedures were approved by the University of Missouri Animal Care and Use Committee. A powdered commercial drug formulation of diminazene diaceturate (Veriben , CevaSante Animale, Libourne, France) was freshly reconstituted with sterile water to a concentration of 7 mg ⁄ mL and the solution was filtered (0.2 micron disk filter; B Braun, Bethlehem, PA, USA) prior to administration. The dose was calculated at 3 mg ⁄ kg diminazene diaceturate (equivalent to 1.68 mg ⁄ kg base or 2.6 mg ⁄ kg of diminazene aceturate). The total volume of reconstituted drug varied from 1.3 to 2.3 mL per cat; all volumes exceeding 2.0 mL were administered in two separate intramuscular (IM) locations. Concentrations of diminazene were measured by highpressure liquid chromatography (HPLC) analysis using UV absorption and ion-pairing conditions. Because the assay detects the amount of diminazene base, it can be used for detection of either diminazene aceturate or diminazene diaceturate. The reference standard of diminazene (Sigma Aldrich, St Louis, MO, USA) was dissolved in distilled water to make up a 1 mg ⁄ mL stock solution. From this stock solution, further dilutions were prepared in distilled water to generate calibration curves in plasma and to generate quality control samples. The calibration curve included eight standards, including zero (blank). The calibration curve linear range was 0.01–10 lg ⁄ mL. The mobile phase consisted of 73% distilled water, 27% acetonitrile, and an ion-pairing reagent added as a mobile phase modifier. As J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2011.01359.x SHORT COMMUNICATION}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Lewis, K. M. and Cohn, L. A. and Birkenheuer, A. J. and Papich, M. G.}, year={2012}, month={Dec}, pages={608–610} }
 @article{lewis_cohn_birkenheuer_papich_2011, title={Pharmacokinetics of diminazene diaceturate in healthy cats}, volume={12}, DOI={10.1111/j.1365-2885.2011.01359}, journal={Journal of Veterinary Pharmacology & Therapeutics}, author={Lewis, K.M. and Cohn, L.A. and Birkenheuer, A.J. and Papich, M.G.}, year={2011}, month={Dec} }
 @article{powers_papich_2011, title={Pharmacokinetics of orally administered phenobarbital in African grey parrots (Psittacus erithacus erithacus)}, volume={34}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2011.01279.x}, abstractNote={Phenobarbital is currently the most frequently prescribed anticonvulsant in small animal medicine, primarily because of its efficacy, long half-life, low expense and safety. Phenobarbital is an anticonvulsant barbiturate, which inhibits seizures at doses lower than those that produce anaesthesia. It is effective as an anticonvulsant in part because of its potentiating action on the inhibitory neurotransmitter gamma aminobutyric acid, which increases the seizure threshold and lowers the electrical activity of the seizure focus. As summarized in reviews, phenobarbital has high oral bioavailability in domestic animals (Vernau & LeCouteur, 2002; Papich, 2009). The drug is highly metabolized via hepatic cytochrome P450 enzymes (Hojo et al., 2002; Vernau & LeCouteur, 2002; Papich, 2009). In dogs, phenobarbital also induces plasma a1-acid glycoprotein, which is the main plasma binding protein for basic drugs (Hojo et al., 2002). The elimination half-life of phenobarbital in humans, dogs and cats has been reported to be 70–100, 37–75 and 35–76 h, respectively. Because of the variability in pharmacokinetics among individuals, therapeutic drug monitoring is recommended to optimize the individual patient dosage (Papich, 2009). Although oral phenobarbital has been investigated in pigeons for the response to external discriminative stimulus (Picker and Poling, 1984; Picker et al., 1986; White et al., 1994), no studies have been reported on the anticonvulsant effects of phenobarbital in birds. The Congo African grey parrot (Psittacus erithacus erithacus) is a popular companion bird, and seizures have been associated with several diseases in this species, including hydrocephalus and hypocalcemia (McDonald, 1988; Fleming et al., 2003; Steinmetz et al., 2008). Because information on pharmacokinetics of phenobarbital in parrots has not been studied, there is no guidance for dosage regimens. This investigation was performed to examine the pharmacokinetics of orally administered phenobarbital in African grey parrots. There was only a small population available (a total of six birds) for study. The total volume of blood that could be harvested from an individual bird for each trial was no more than approximately 4–5 mL, limiting the number of blood draws possible because of the minimum plasma volume requirement for drug assay. Therefore, our objective was to present this as a preliminary report that can potentially serve as a basis for further study. Five privately owned Congo African grey parrots of mixed gender ranging in age from 4 to 22 years and in weight from 0.381 to 0.536 kg on varied diets that had never previously received phenobarbital were determined to be in good health based on physical examination, haematology and plasma biochemistries. Birds were allowed to drink and feed ad libitum during the study period. Phenobarbital solution was extemporaneously prepared using modifications from a previous report (Cober & Johnson, 2007). A 30 mg ⁄ mL solution was prepared by crushing 64.8-mg tablets and mixing with equal portions of Ora-Plus and Ora-Sweet (Paddock Laboratories, Minneapolis, MN, USA). Birds were administered a single oral dose of 17 mg ⁄ kg phenobarbital directly per os (PO). The dosage used was the highest dosage administered to a single sentinel African grey parrot with seizures of unknown cause without clinical response to phenobarbital administration and suboptimal plasma concentrations determined through periodic monitoring. Blood samples (0.40 mL ⁄ sample) were collected from the right jugular vein using a 25 g 5 ⁄ 8 inch needle on a 1-mL syringe prior to drug administration and at 1, 2, 4, 6 and 8 h after drug administration. After collection, blood samples were placed into tubes coated with lithium heparin (BD Microtainer, Franklin Lakes, NJ, USA). Samples were immediately centrifuged (12 000 g) for 90 sec and the plasma decanted and delivered on ice to the laboratory within 24 h for processing. Because of the high degree of variability in plasma concentrations of phenobarbital among birds in the first trial, a second trial was performed with a solution, rather than a suspension with the goal of producing more consistent oral absorption with the drug dissolved in the formulation. Four of the five birds in the second trial had been used in the first trial, with a ten-week wash-out period in between trials. In the second trial, a solution was extemporaneously prepared by combining 1 mL of injectable phenobarbital solution (130 mg ⁄ mL; Baxter Healthcare Corp, Deerfield, IL, USA) with 12-mL glycerine for a final concentration of 10 mg ⁄ mL. Birds were fasted for 8 h or more prior to and during the drug trial, and were administered drug by intracrop gavage using a ball-tipped stainless steel feeding tube (GA). The feeding tube was flushed after drug delivery with J. vet. Pharmacol. Therap. 34, 615–617. doi: 10.1111/j.1365-2885.2011.01279.x. SHORT COMMUNICATION}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Powers, L. V. and Papich, M. G.}, year={2011}, month={Dec}, pages={615–617} }
 @article{ratzlaff_papich_flammer_2011, title={Plasma Concentrations of Fluconazole After a Single Oral Dose and Administration in Drinking Water in Cockatiels (Nymphicus hollandicus)}, volume={25}, ISSN={["1082-6742"]}, DOI={10.1647/2009-044.1}, abstractNote={Abstract Candidiasis frequently affects the oropharynx, esophagus, and crop of juvenile birds with immature immune systems and adult birds that have received long-term antibiotic treatment. Fluconazole is used extensively in human medicine to treat mucosal and invasive candidiasis and has been used in birds; however, there have been few pharmacokinetic studies in avian species to guide safe and effective treatment. The purpose of the present study was to investigate the disposition of fluconazole in cockatiels (Nymphicus hollandicus) after single oral dose administration and to determine if therapeutic plasma concentrations could be safely achieved by providing medicated water. Twenty-eight cockatiels were placed into 7 groups and were orally administered a 10 mg/kg fluconazole suspension. Blood samples were collected from each group for plasma fluconazole assay at serial time points. Fluconazole-medicated drinking water was prepared daily and offered to 15 cockatiels at a concentration of 100 mg/L for 8 days. Blood was collected for plasma fluconazole assay at 2 time points on days 3 and 7. When using naïve averaged data in the single-dose study, pharmacokinetic parameters were similar for both compartmental and noncompartmental analyses. The elimination half-life of fluconazole was 19.01 hours, maximum plasma concentration was 4.94 μg/mL, time until maximal concentration was 3.42 hours, and the area under the plasma concentration versus time curve (AUC) was 149.28 h × μg/mL. Computer-simulated trough and peak plasma concentrations at steady-state after multiple doses of fluconazole at 10 mg/kg every 24 hours, 10 mg/kg every 48 hours, and 5 mg/kg every 24 hours were approximately 4.1–8.5 μg/mL, 1.2–6.0 μg/mL, and 2.0–4.3 μg/mL, respectively. Mean ± SD plasma fluconazole concentrations for the 100 mg/L medicated water study at 0800 and 1600 hours on day 3 were 3.69 ± 1.22 µg/mL (range, 1.73–5.26 µg/mL) and 4.17 ± 1.96 µg/mL (range, 3.58–7.49 µg/mL), respectively, and at 0800 and 1600 hours on day 7 were 4.78 ± 0.91 µg/mL (range, 2.62–6.11 µg/mL) and 6.61 ± 1.67 µg/mL (range, 3.76–8.78 µg/mL), respectively. Treatment with fluconazole administered orally at a dosage of 5 mg/kg once daily or 10 mg/kg every 48 hours or fluconazole administered in the drinking water at a concentration of 100 mg/L is predicted to maintain plasma concentrations in most cockatiels that exceed the minimum inhibitory concentration of 90% or therapeutic AUC ∶ MIC of most strains of Candida albicans (by using susceptibility data from humans). The compounded oral suspension was stable for 14 days when stored at 5°C (41°F) and protected from light.}, number={1}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Ratzlaff, Katherine and Papich, Mark G. and Flammer, Keven}, year={2011}, month={Mar}, pages={23–31} }
 @article{levine_papich_gookin_davidson_davis_hayes_2011, title={Ronidazole pharmacokinetics after intravenous and oral immediate-release capsule administration in healthy cats}, volume={13}, ISSN={["1532-2750"]}, DOI={10.1016/j.jfms.2010.12.001}, abstractNote={Ronidazole (RDZ) is an effective treatment for feline Tritrichomonas foetus infection, but has produced neurotoxicity in some cats. An understanding of the disposition of RDZ in cats is needed in order to make precise dosing recommendations. Single-dose pharmacokinetics of intravenous (IV) RDZ and immediate-release RDZ capsules were evaluated. A single dose of IV RDZ (mean 9.2 mg/kg) and a 95 mg immediate-release RDZ capsule (mean 28.2 mg/kg) were administered to six healthy cats in a randomized crossover design. Plasma samples were collected for 48 h and assayed for RDZ using high pressure liquid chromatography (HPLC). Systemic absorption of oral RDZ was rapid and complete, with detection in the plasma of all cats by 10 min after dosing and a bioavailability of 99.64 (±16.54)%. The clearance of RDZ following IV administration was 0.82 (±0.07) ml/kg/min. The terminal half-life was 9.80 (±0.35) and 10.50 (±0.82) h after IV and oral administration, respectively, with drug detectable in all cats 48 h after both administrations. The high oral bioavailability of RDZ and slow elimination may predispose cats to neurotoxicity with twice-daily administration. Less frequent administration should be considered for further study of effective treatment of T foetus-infected cats.}, number={4}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={LeVine, Dana N. and Papich, Mark G. and Gookin, Jody L. and Davidson, Gigi S. and Davis, Jennifer L. and Hayes, Rebecca B.}, year={2011}, month={Apr}, pages={244–250} }
 @book{papich_2011, place={St. Louis, Missouri}, edition={Third}, title={Saunders Handbook of Veterinary Drugs}, publisher={Elsevier-Saunders}, author={Papich, M.G.}, year={2011} }
 @article{innis_ceresia_merigo_weber_papich_2012, title={Single-dose pharmacokinetics of ceftazidime and fluconazole during concurrent clinical use in cold-stunned Kemp's ridley turtles (Lepidochelys kempii)}, volume={35}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2011.01290.x}, abstractNote={Innis, C. J., Ceresia, M. L., Merigo, C., Scott Weber III, E., Papich, M. G. Single‐dose pharmacokinetics of ceftazidime and fluconazole during concurrent clinical use in cold‐stunned Kemp’s ridley turtles (Lepidochelys kempii). J. vet. Pharmacol. Therap. 35, 82–89.Single‐dose pharmacokinetics of intramuscularly administered ceftazidime (22 mg/kg) and subcutaneously administered fluconazole (21 mg/kg) were investigated during concurrent clinical use in naturally cold‐stunned Kemp’s ridley turtles (Lepidochelys kempii). Maximum mean concentration for ceftazidime was 61.31 μg/mL, and time of maximum concentration was 1.56 h postinjection. Maximum mean concentration for fluconazole was 26.16 μg/mL, and time of maximum concentration was 0.79 h postinjection. Results indicate that the ceftazidime dose and dosing interval used in this study are likely to be effective in treating susceptible strains of bacteria in Kemp’s ridley turtles. However, the fluconazole dose and dosing interval are not likely to be effective against filamentous fungal pathogens that are often involved in marine turtle fungal infections.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Innis, C. J. and Ceresia, M. L. and Merigo, C. and Weber, E. Scott, III and Papich, M. G.}, year={2012}, month={Feb}, pages={82–89} }
 @inbook{papich_2010, place={St. Louis, Missouri, USA}, edition={7th}, title={Antibacterial Drug Therapy}, booktitle={Textbook of Veterinary Internal Medicine}, publisher={Saunders Elsevier}, author={Papich, M.G.}, editor={Ettinger, S.J. and Feldman, E.C.Editors}, year={2010}, pages={589–595} }
 @misc{papich_2010, title={Clarification on drugs used to treat leishmaniasis}, volume={237}, number={5}, journal={Journal of the American Veterinary Medical Association}, author={Papich, M. G.}, year={2010}, pages={493–493} }
 @article{papich_2010, title={Clarification on drugs used to treat leishmaniasis}, volume={237}, number={5}, journal={Journal of the American Veterinary Medical Association}, author={Papich, M.G.}, year={2010}, month={Sep}, pages={493} }
 @article{musulin_mariani_papich_2011, title={Diazepam pharmacokinetics after nasal drop and atomized nasal administration in dogs}, volume={34}, ISSN={["1365-2885"]}, url={http://dx.doi.org/10.1111/j.1365-2885.2010.01186.x}, DOI={10.1111/j.1365-2885.2010.01186.x}, abstractNote={Musulin, S. E., Mariani, C. L., Papich, M. G. Diazepam pharmacokinetics after nasal drop and atomized nasal administration in dogs.J. vet. Pharmacol. Therap.34, 17–24.The standard of care for emergency therapy of seizures in veterinary patients is intravenous (i.v.) administration of benzodiazepines, although rectal administration of diazepam is often recommended for out‐of‐hospital situations, or when i.v. access has not been established. However, both of these routes have potential limitations. This study investigated the pharmacokinetics of diazepam following i.v., intranasal (i.n.) drop and atomized nasal administration in dogs. Six dogs were administered diazepam (0.5 mg/kg) via all three routes following a randomized block design. Plasma samples were collected and concentrations of diazepam and its active metabolites, oxazepam and desmethyldiazepam were quantified with high‐performance liquid chromatography (HPLC). Mean diazepam concentrations >300 ng/mL were reached within 5 min in both i.n. groups. Diazepam was converted into its metabolites within 5 and 10 min, respectively, after i.v. and i.n. administration. The half lives of the metabolites were longer than that of the parent drug after both routes of administration. The bioavailability of diazepam after i.n. drop and atomized nasal administration was 42% and 41%, respectively. These values exceed previously published bioavailability data for rectal administration of diazepam in dogs. This study confirms that i.n. administration of diazepam yields rapid anticonvulsant concentrations of diazepam in the dog before a hepatic first‐pass effect.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Musulin, S. E. and Mariani, C. L. and Papich, M. G.}, year={2011}, month={Feb}, pages={17–24} }
 @misc{smith_papich_russell_mitchell_2010, title={EFFECTS OF COMPOUNDING ON PHARMACOKINETICS OF ITRACONAZOLE IN BLACK-FOOTED PENGUINS (SPHENISCUS DEMERSUS)}, volume={41}, ISSN={["1042-7260"]}, DOI={10.1638/2010-0019.1}, abstractNote={Abstract Itraconazole is used to treat and prevent aspergillosis in captive penguin colonies. Although commercial formulations of itraconazole are available, compounding is sometimes performed to decrease cost or to provide a different concentration of the drug. Using a two-way crossover design, the pharmacokinetics of both a commercially available oral itraconazole solution and a compounded oral itraconazole solution were compared in six black-footed penguins (Spheniscus demersus). Each itraconazole formulation was administered orally in frozen–thawed capelin at 7 mg/kg. Plasma itraconazole concentrations at time 0 (pretreatment), 20 and 40 min post–drug administration, and 1, 2, 4, 6, 8, and 12 hr post–drug administration were determined using reverse-phase high-performance liquid chromatography. Drug concentrations were analyzed using standard pharmacokinetic methods. Plasma clearance of the commercial itraconazole solution was more rapid than the clearance published for other species, possibly warranting more frequent dosing in black-footed penguins. Absorption of itraconazole, as determined by peak concentration and area under the curve, was significantly higher for the commercial formulation when compared to the compounded formulation, likely as a result of the presence of cyclodextrin, a carrier compound shown to improve oral absorption, in the commercial formulation. Extrapolating dosing regimens for compounded itraconazole formulations from regimens determined for commercial formulations warrants caution as a result of the significant differences in pharmacokinetics.}, number={3}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Smith, Joseph A. and Papich, Mark G. and Russell, Gregg and Mitchell, Mark A.}, year={2010}, month={Sep}, pages={487–495} }
 @article{brainard_epstein_lobato_kwon_papich_moore_2011, title={Effects of Clopidogrel and Aspirin on Platelet Aggregation, Thromboxane Production, and Serotonin Secretion in Horses}, volume={25}, ISSN={["0891-6640"]}, DOI={10.1111/j.1939-1676.2010.0647.x}, abstractNote={Background:Critically ill horses are susceptible to thrombotic disease, which might be related to increased platelet reactivity and activation.Objectives:To compare the effect of oral clopidogrel and aspirin (ASA) on equine platelet function.Animals:Six healthy adult horses.Methods:Horses received clopidogrel (2 mg/kg PO q24h) or ASA (5 mg/kg PO q24h) for 5 days in a prospective randomized cross‐over design. Platelet aggregation responses to adenosine diphosphate (ADP) and collagen via optical aggregometry, and platelet secretion of serotonin (5HT) and production of thromboxane B2(TXB2) by ELISA were evaluated. In horses receiving clopidogrel, high‐performance liquid chromatography analysis for clopidogrel and its carboxylic‐acid metabolite SR 26334 was performed.Results:SR 26334 was identified in all clopidogrel‐treated horses, although the parent compound was not detected. Clopidogrel resulted in decreases in ADP‐induced platelet aggregation persisting for 120 hours after the final dose. ADP‐induced platelet aggregation decreased from a baseline of 70.2 ± 14.7% to a minimum of 15.9 ± 7.7% 24 hours after the final dose (P< .001). Collagen‐induced aggregation decreased from a baseline of 93 ± 9.5% to a minimum of 70.8 ± 16.9% 48 hours after the final dose (P< .001). ASA did not decrease platelet aggregation with either agonist. ASA decreased serum TXB2from a baseline value of 1310 ± 1045 to 128 ± 64 pg/mL within 24 hours (P< .01).Conclusions and Clinical Importance:Clopidogrel effectively decreases ADP‐induced platelet aggregation in horses, and could have therapeutic applications for equine diseases associated with platelet activation.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Brainard, B. M. and Epstein, K. L. and LoBato, D. and Kwon, S. and Papich, M. G. and Moore, J. N.}, year={2011}, pages={116–122} }
 @article{tolbert_bissett_king_davidson_papich_peters_degernes_2010, title={Efficacy of Oral Famotidine and 2 Omeprazole Formulations for the Control of Intragastric pH in Dogs}, volume={25}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/j.1939-1676.2010.0651.x}, DOI={10.1111/j.1939-1676.2010.0651.x}, abstractNote={Background:  Little is known about the efficacy of commonly used acid suppressants on intragastric pH in dogs.Objective:  To compare the effect of oral famotidine, 2 formulations of omeprazole, and placebo on intragastric pH in dogs with a catheter‐free, continuous pH monitoring system.Animals:  Six healthy adult mixed‐breed colony dogs.Methods:  Utilizing a randomized, 4‐way cross over, open‐label study, dogs were administered famotidine PO (1.0–1.3 mg/kg q12h), omeprazole tablet (1.5–2.6 mg/kg q24h), omeprazole reformulated paste (RP) (Gastrogard, 1.5–2.6 mg/kg q24h), and placebo for 7 days followed by a 10‐day washout period. Radiotelemetric pH capsules were placed with gastroscopy assistance to continuously record intragastric pH for 4 days (days 4–7 of dosing). The percentage of time that intragastric pH was ≥3 and ≥4 was compared among treatment groups using repeated measures of analysis of variance. Tukey's Studentized range test was used to determine which groups were different with α= 0.05.Results:  Mean ± SD percent time intragastric pH was ≥3 and ≥4 was 22 ± 8% and 14 ± 6% for famotidine, 63 ± 14% and 52 ± 17% for omeprazole tablet, 54 ± 17% and 44 ± 18% for omeprazole RP, and 6 ± 6% and 5 ± 5% for placebo. Both omeprazole formulations significantly increased intragastric pH compared with famotidine and placebo, but omeprazole tablet and RP was not significantly different from each other.Conclusion:  Oral omeprazole tablet and RP provide superior gastric acid suppression to famotidine, and should therefore be considered more effective for the treatment of acid related disorders in dogs.}, number={1}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Tolbert, K. and Bissett, S. and King, A. and Davidson, G. and Papich, M. and Peters, E. and Degernes, L.}, year={2010}, month={Dec}, pages={47–54} }
 @article{burns_morrow_gilley_papich_2010, title={Evaluation of Pharmacokinetic-Pharmacodynamic Relationships for BioRelease Meloxicam Formulations in Horses}, volume={30}, ISSN={["1542-7412"]}, DOI={10.1016/j.jevs.2010.09.004}, abstractNote={The present study was designed to evaluate the pharmacokinetic-pharmacodynamic relationships for three controlled release meloxicam formulations in horses so as to select one for continued clinical evaluation. Twelve mature research horses of various light breeds were randomly assigned to one of the three treatment groups (n = 4 horses per group). Each horse received two consecutive intramuscular injections at 0 and 72 hours, containing 1,500 mg in 2 mL of one of three experimental BioRelease meloxicam formulations designed to maintain therapeutic blood concentrations (0.15–0.2 μg/mL) for 48 to 96 hours. Blood samples were collected pre and post-treatment. Injection site (0–3) and general well-being (normal or abnormal – with description) were recorded at the time of each blood collection. The plasma concentration-time curve for each horse was analyzed separately to estimate standard noncompartmental pharmacokinetic variables. Results from the present study suggest that potential therapeutic advantages of meloxicam may be enhanced by applying recent advances in biodegradable controlled release drug delivery, allowing single administration products to replace multiple daily treatment protocols.}, number={10}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Burns, Patrick J. and Morrow, Chris and Gilley, Richard M. and Papich, Mark G.}, year={2010}, month={Oct}, pages={539–544} }
 @article{hardie_lascelles_meuten_davidson_papich_hansen_2011, title={Evaluation of intermittent infusion of bupivacaine into surgical wounds of dogs postoperatively}, volume={190}, ISSN={["1090-0233"]}, url={https://dx.doi.org/10.1016/j.tvjl.2010.11.008}, DOI={10.1016/j.tvjl.2010.11.008}, abstractNote={Thirty-one dogs were randomised to receive intermittent wound infusion of bupivacaine or saline after surgery. Wound pressure sensitivity, pain scores, body temperature, heart rate, respiratory rate, analgesic drugs administered, time to walking and time to eating after surgery were recorded. Plasma bupivacaine concentrations were measured. The relative frequency distributions of the non-interventional and interventional pain scores, but not the relative frequency distributions of palpation pain scores or wound pressure sensitivity, were significantly different between groups following surgery. There was a significant difference between groups in the time to eating and in the amount and timing of analgesic drugs administered. Measured plasma bupivacaine concentrations demonstrated systemic absorption of the drug. Bupivacaine infusion into surgical wounds after surgery may improve post-operative recovery, but no effect on wound tenderness was demonstrated in this study.}, number={2}, journal={VETERINARY JOURNAL}, author={Hardie, Elizabeth M. and Lascelles, B. Duncan X. and Meuten, Travis and Davidson, Gigi S. and Papich, Mark G. and Hansen, Bernie D.}, year={2011}, month={Nov}, pages={287–289} }
 @article{apley_claxton_davis_deveau_donecker_lucas_neal_papich_2010, title={Exploration of developmental approaches to companion animal antimicrobials: Providing for the unmet therapeutic needs of dogs and cats}, volume={33}, number={2}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Apley, M. and Claxton, R. and Davis, C. and DeVeau, I. and Donecker, J. and Lucas, A. and Neal, A. and Papich, M.}, year={2010}, pages={196–201} }
 @article{moore_munana_papich_nettifee-osborne_2010, title={Levetiracetam pharmacokinetics in healthy dogs following oral administration of single and multiple doses}, volume={71}, ISSN={["1943-5681"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-77950965044&partnerID=MN8TOARS}, DOI={10.2460/ajvr.71.3.337}, abstractNote={Abstract
Objective—To measure pharmacokinetics of levetiracetam (LEV) after single-dose oral administration in healthy dogs and determine whether pharmacokinetics changed after repeated oral dosing.
Animals—6 healthy adult dogs.
Procedures—Pharmacokinetics were calculated following administration of a single dose (mean, 21.7 mg/kg, PO; day 1) and after administration of the last dose following administration for 6 days (20.8 to 22.7 mg/kg, PO, q 8 h; days 2 to 7). Plasma LEV concentrations were determined by use of high-pressure liquid chromatography. Pharmacokinetic data were analyzed by use of a 1-compartment model with first-order absorption.
Results—Peak concentration occurred 0.6 hours after administration of the first dose, with an absorption half-life of 0.06 hours. Minimal accumulation occurred over the 7 days, with only a slight increase in total area under the concentration-versus-time curve from 268.52 ± 56.33 h·μg/mL (mean ± SD) to 289.31 ± 51.68 h·μg/mL after 7 days. Terminal half-life was 2.87 ± 0.21 hours after the first dose and 3.59 ± 0.82 hours after the last dose on day 7. Trough plasma concentrations were variable, depending on the time of day they were measured (morning trough concentration, 18.42 ± 5.16 μg/mL; midday trough concentration, 12.57 ± 4.34 μg/mL), suggesting a diurnal variation in drug excretion.
Conclusions and Clinical Relevance—Results indicated that the pharmacokinetics of LEV did not change appreciably after administration of multiple doses over 7 days. Administration of LEV at a dosage of 20 mg/kg, PO, every 8 hours to healthy dogs yielded plasma drug concentrations consistently within the therapeutic range established for LEV in humans.}, number={3}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Moore, Sarah A. and Munana, Karen R. and Papich, Mark G. and Nettifee-Osborne, Julie}, year={2010}, month={Mar}, pages={337–341} }
 @article{schnabel_papich_watts_fortier_2010, title={Orally administered doxycycline accumulates in synovial fluid compared to plasma}, volume={42}, ISSN={["2042-3306"]}, DOI={10.2746/042516409x478514}, abstractNote={SummaryReasons for performing study:Tetracycline compounds have been used to slow the progression of osteoarthritis (OA) and rheumatoid arthritis but the concentration of doxycycline attained in synovial fluid following oral, low‐dose administration has yet to be determined.Objective:To determine the concentration of doxycycline in synovial fluid following oral, low‐dose administration.Methods:Six mature horses received doxycycline (5 mg/kg bwt q. 12 h for 5 doses). Venous blood and synovial fluid samples were collected at t = 0, 0.25, 0.5, 1, 12, 24, 48 and 72 h. Doxycycline concentrations were measured using reverse phase high pressure liquid chromatography with ultraviolet detection.Results:Doxycycline concentrations at all time points after t = 0 were above the lower limit of quantification for the assay. Plasma concentrations of doxycycline were above 0.21 µg/ml at t = 0.5 h. The mean ± s.d. peak concentration (Cmax) of doxycycline in plasma was 0.37 ± 0.22 µg/ml and time to peak concentration was 0.54 ± 0.19 h. Synovial fluid concentrations of doxycycline were above 0.12 µg/ml 1 h after drug administration. The mean Cmaxof doxycycline in the synovial fluid was 0.27 ± 0.10 µg/ml. The penetration factor of doxycycline from plasma into synovial fluid, as determined by a ratio of the area‐under‐the‐curve for synovial fluid:plasma during the sampling period, was 4.6.Potential relevance:Orally administered doxycycline distributes easily into synovial fluid with a penetration factor of 4.6. Terminal half‐life of the drug in synovial fluid was longer than in the plasma, indicating possible accumulation in this compartment. Furtherin vivostudies are warranted to define a medication protocol prior to routine clinical use of doxycycline for the treatment of OA.}, number={3}, journal={EQUINE VETERINARY JOURNAL}, author={Schnabel, L. V. and Papich, M. G. and Watts, A. E. and Fortier, L. A.}, year={2010}, month={Apr}, pages={208–212} }
 @article{brainard_kleine_papich_budsberg_2010, title={Pharmacodynamic and pharmacokinetic evaluation of clopidogrel and the carboxylic acid metabolite SR 26334 in healthy dogs}, volume={71}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.71.7.822}, abstractNote={Abstract
Objective—To determine pharmacodynamic and pharmacokinetic properties of clopidogrel and the metabolite SR 26334 in dogs.
Animals—9 mixed-breed dogs.
Procedures—8 dogs received clopidogrel (mean ± SD 1.13 ± 0.17 mg/kg, PO, q 24 h) for 3 days; 5 of these dogs subsequently received a lower dose of clopidogrel (0.5 ± 0.18 mg/kg, PO, q 24 h) for 3 days. Later, 5 dogs received clopidogrel (1.09 ± 0.12 mg/kg, PO, q 24 h) for 5 days. Blood samples were collected for optical platelet aggregometry, citrated native and platelet mapping thrombelastography (TEG), and measurement of plasma drug concentrations. Impedance aggregometry was performed on samples from 3 dogs in each 3-day treatment group.
Results—ADP-induced platelet aggregation decreased (mean ± SD 93 ± 6% and 80 ± 22% of baseline values, respectively) after 72 hours in dogs in both 3-day treatment groups; duration of effect ranged from > 3 to > 7 days. Platelet mapping TEG and impedance aggregometry yielded similar results. Citrated native TEG was not different among groups. Clopidogrel was not detected in any samples; in dogs given 1.13 ± 0.17 mg/kg, maximum concentration of SR 26334 (mean ± SD, 0.206 ± 0.2 μg/mL) was detected 1 hour after administration.
Conclusions and Clinical Relevance—Clopidogrel inhibited ADP-induced platelet aggregation in healthy dogs and may be a viable antiplatelet agent for use in dogs.
Impact for Human Medicine—Pharmacodynamic effects of clopidogrel in dogs were similar to effects reported in humans; clopidogrel may be useful in studies involving dogs used to investigate human disease.}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Brainard, Benjamin M. and Kleine, Stephanie A. and Papich, Mark G. and Budsberg, Steven C.}, year={2010}, month={Jul}, pages={822–830} }
 @article{yamarik_wilson_wiebe_pusterla_edman_papich_2010, title={Pharmacokinetics and toxicity of ciprofloxacin in adult horses}, volume={33}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2010.01167.x}, abstractNote={Using a randomized, cross-over study design, ciprofloxacin was administered i.g. to eight adult mares at a dose of 20 mg/kg, and to seven of the eight horses at a dose of 5 mg/kg by bolus i.v. injection. The mean C(0) was 20.5 μg/mL (±8.8) immediately after i.v. administration. The C(max) was 0.6 μg/mL (±0.36) at T(max) 1.46 (±0.66) h after the administration of oral ciprofloxacin. The mean elimination half-life after i.v. administration was 5.8 (±1.6) h, and after oral administration the terminal half-life was 3.6 (±1.7) h. The overall mean systemic availability of the oral dose was 10.5 (±2.8)%. Transient adverse effects of mild to moderate severity included agitation, excitement and muscle fasciculation, followed by lethargy, cutaneous edema and loss of appetite developed in all seven horses after i.v. administration. All seven horses developed mild transient diarrhea at 36-48 after i.v. dosing. All eight horses dosed intragastrically experienced adverse events attributable to ciprofloxacin administration. Adverse events included mild transient diarrhea to severe colitis, endotoxemia and laminitis necessitating euthanasia of three horses on humane grounds. The high incidences of adverse events preclude oral and rapid i.v. push administration of ciprofloxacin.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Yamarik, T. A. and Wilson, W. D. and Wiebe, V. J. and Pusterla, N. and Edman, J. and Papich, M. G.}, year={2010}, month={Dec}, pages={587–594} }
 @article{divers_papich_mcbride_stedman_perpinan_koch_hernandez_barron_pethel_budsberg_et al._2010, title={Pharmacokinetics of meloxicam following intravenous and oral administration in green iguanas (Iguana iguana)}, volume={71}, DOI={10.2460/ajvr.71.11.1277}, abstractNote={Abstract
Objective—To determine pharmacokinetics of meloxicam in healthy green iguanas following PO and IV administration and assess potential toxicity.
Animals—21 healthy green iguanas (Iguana iguana).
Procedures—To assess pharmacokinetics, 13 iguanas were administered a single dose (0.2 mg/kg) of meloxicam PO and, 14 days later, the same dose IV. To assess potential toxicity, 4 iguanas were given meloxicam at a dosage of 1 or 5 mg/kg, PO, every 24 hours for 12 days, and results of histologic examination were compared with results for another 4 iguanas given a single dose of meloxicam (0.2 mg/kg).
Results—There were no significant differences between PO and IV administration with regard to terminal half-life (mean ± SD, 12.96 ± 8.05 hours and 9.93 ± 4.92 hours, respectively), mean area under the curve to the last measured concentration (5.08 ± 1.62 μg•h/mL and 5.83 ± 2.49 μg•h/mL), volume of distribution (745 ± 475 mL/kg and 487 ± 266 mL/kg), or clearance (40.17 ± 10.35 mL/kg/h and 37.17 ± 16.08 mL/kg/h). Maximum plasma concentration was significantly greater following IV (0.63 ± 0.17 μg/mL) versus PO (0.19 ± 0.07 μg/mL) administration. Time from administration to maximum plasma concentration and mean residence time were significantly longer following PO versus IV administration. Daily administration of high doses (1 or 5 mg/kg) for 12 days did not induce any histologic changes in gastric, hepatic, or renal tissues.
Conclusions and Clinical Relevance—Results suggested that administration of meloxicam at a dose of 0.2 mg/kg IV or PO in green iguanas would result in plasma concentrations > 0.1 μg/mL for approximately 24 hours. (Am J Vet Res 2010;71:1277–1283)}, number={11}, journal={American Journal of Veterinary Research}, author={Divers, S. J. and Papich, Mark and McBride, M. and Stedman, N. L. and Perpinan, D. and Koch, T. F. and Hernandez, S. M. and Barron, G. H. and Pethel, M. and Budsberg, S. C. and et al.}, year={2010}, pages={1277–1283} }
 @article{guzman_flammer_papich_grooters_shaw_applegate_tully_2010, title={Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis)}, volume={71}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.71.4.460}, abstractNote={Abstract
Objective—To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).
Animals—15 clinically normal adult Hispaniolan Amazon parrots.
Procedures—Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial.
Results—Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (Cmax) and area under the curve (AUC). In the multiple-dose trial, Cmax, AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident.
Conclusions and Clinical Relevance—In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.}, number={4}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Guzman, David Sanchez-Migallon and Flammer, Keven and Papich, Mark G. and Grooters, Amy M. and Shaw, Shannon and Applegate, Jeff and Tully, Thomas N., Jr.}, year={2010}, month={Apr}, pages={460–467} }
 @article{papich_davis_floerchinger_2010, title={Pharmacokinetics, protein binding, and tissue distribution of orally administered cefpodoxime proxetil and cephalexin in dogs}, volume={71}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.71.12.1484}, DOI={10.2460/ajvr.71.12.1484}, abstractNote={Abstract
Objective—To determine the effect of protein binding on the pharmacokinetics and distribution from plasma to interstitial fluid (ISF) of cephalexin and cefpodoxime proxetil in dogs.
Animals—6 healthy dogs.
Procedures—In a crossover study design, 25 mg of cephalexin/kg or 9.6 mg of cefpodoxime/kg was administered orally. Blood samples were collected before (time 0) and 0.33, 0.66, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours after treatment. An ultrafiltration device was used in vivo to collect ISF at 0, 2, 4, 6, 8, 10, 12, 16, and 24 hours. Plasma and ISF concentrations were analyzed with high-pressure liquid chromatography. Plasma protein binding was measured by use of a microcentrifugation technique.
Results—Mean plasma protein binding for cefpodoxime and cephalexin was 82.6% and 20.8%, respectively. Mean ± SD values for cephalexin in plasma were determined for peak plasma concentration (Cmax, 31.5 ± 11.5 μg/mL), area under the time-concentration curve (AUC, 155.6 ± 29.5 μg•h/mL), and terminal half-life (T½, 4.7 ± 1.2 hours); corresponding values in ISF were 16.3 ± 5.8 μg/mL, 878 ± 21.0 μg•h/mL, and 3.2 ± 0.6 hours, respectively. Mean ± SD values for cefpodoxime in plasma were 33.0 ± 6.9 μg/mL (Cmax), 282.8 ± 44.0 μg•h/mL (AUC), and 5.7 ± 0.9 hours (T1/2); corresponding values in ISF were 4.3 ± 2.0 μg/mL, 575 ± 174 μg•h/mL, and 10.4 ± 3.3 hours, respectively.
Conclusions and Clinical Relevance—Tissue concentration of protein-unbound cefpodoxime was similar to that of the protein-unbound plasma concentration. Cefpodoxime remained in tissues longer than did cephalexin.}, number={12}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Papich, Mark G. and Davis, Jennifer L. and Floerchinger, Amanda M.}, year={2010}, month={Dec}, pages={1484–1491} }
 @misc{papich_2010, title={Proposed changes to Clinical Laboratory Standards Institute interpretive criteria for methicillin-resistant Staphylococcus pseudintermedius isolated from dogs}, volume={22}, number={1}, journal={Journal of Veterinary Diagnostic Investigation}, author={Papich, M. G.}, year={2010}, pages={160–160} }
 @article{papich_2010, title={Proposed changes to Clinical Laboratory Standards Institute interpretive criteria for methicillin-resistant Staphylococcus pseudintermedius isolated from dogs}, volume={22}, number={1}, journal={Journal of Veterinary Diagnostic Investigation}, author={Papich, M.G.}, year={2010}, month={Jan}, pages={160} }
 @article{howard_papich_felt_long_mckeon_bond_torreilles_luong_green_2010, title={The Pharmacokinetics of Enrofloxacin in Adult African Clawed Frogs (Xenopus laevis)}, volume={49}, number={6}, journal={Journal American Association Laboratory Animal Science}, author={Howard, A.M. and Papich, M.G. and Felt, S.A. and Long, C.T. and McKeon, G.P. and Bond, E.S. and Torreilles, S.L. and Luong, R.H. and Green, S.L.}, year={2010}, pages={800–4} }
 @article{davis_marshall_papich_blikslager_campbell_2011, title={The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses}, volume={34}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/j.1365-2885.2010.01185.x}, DOI={10.1111/j.1365-2885.2010.01185.x}, abstractNote={Davis, J. L., Marshall, J. F., Papich, M. G., Blikslager, A. T., Campbell, N. B. The pharmacokinetics and in vitro cyclooxygenase selectivity of deracoxib in horses. J. vet. Pharmacol. Therap.34, 12–16.The purpose of this study was to determine the pharmacokinetics of deracoxib following oral administration to horses. In addition, in vitro equine whole blood cyclooxygenase (COX) selectivity assays were performed. Six healthy adult horses were administered deracoxib (2 mg/kg) orally. Plasma samples were collected prior to drug administration (time 0), and 10, 20, 40 min and 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after administration for analysis with high pressure liquid chromatography using ultraviolet detection. Following PO administration, deracoxib had a long elimination half‐life (t1/2k10) of 12.49 ± 1.84 h. The average maximum plasma concentration (Cmax) was 0.54 μg/mL, and was reached at 6.33 ± 3.44 h. Bioavailability was not determined because of the lack of an IV formulation. Results of in vitro COX selectivity assays showed that deracoxib was selective for COX‐2 with a COX‐1/COX‐2 ratio of 25.67 and 22.06 for the IC50 and IC80, respectively. Dosing simulations showed that concentrations above the IC80 for COX‐2 would be maintained following 2 mg/kg PO q12h, and above the IC50 following 2 mg/kg PO q24h. This study showed that deracoxib is absorbed in the horse after oral administration, and may offer a useful alternative for anti‐inflammatory treatment of various conditions in the horse.}, number={1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Davis, J. L. and Marshall, J. F. and Papich, M. G. and Blikslager, A. T. and Campbell, N. B.}, year={2011}, month={Jan}, pages={12–16} }
 @article{moore_muñana_papich_nettifee osborne_2011, title={The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital}, volume={34}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/j.1365-2885.2010.01188.x}, DOI={10.1111/j.1365-2885.2010.01188.x}, abstractNote={Moore, S.A., Muñana, K.R., Papich, M.G., Nettifee‐Osborne, J.A. The pharmacokinetics of levetiracetam in healthy dogs concurrently receiving phenobarbital.J. vet. Pharmacol. Therap.34, 31–34.Levetiracetam (LEV) is a commonly used add‐on medication in dogs with refractory epilepsy. The objective of this study was to determine if the pharmacokinetics of LEV are altered by concurrent administration of phenobarbital (PB). Six healthy dogs received a single oral dose of LEV (16.7–27.8 mg/kg). Blood samples were collected at baseline and intermittently for 24 h. The study was repeated after the dogs received oral PB (2.0–3.3 mg/kg) twice daily for 21 days. Plasma LEV levels were evaluated by high pressure liquid chromatography, and data analyzed using a compartmental model. Compared with values determined when LEV was administered alone, concurrent administration of PB resulted in a decrease in LEV peak concentration (Cmax) from 32.39 ± 6.76 to 18.22 ± 8.97 (P = 0.0071), a decrease in elimination half‐life (T1/2) from 3.43 ± 0.47 to 1.73 ± 0.22 (P = 0.0005), and an increase in oral clearance from 124.93 ± 26.93 to 252.99 ± 135.43 ml/h/kg (P < 0.0001). Concurrent PB administration significantly alters the pharmacokinetics of LEV in the dog, indicating that dosage adjustments might be necessary when the drug is administered with PB.}, number={1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Moore, S.A. and Muñana, K.R. and Papich, M.G. and Nettifee Osborne, J.A.}, year={2011}, month={Jan}, pages={31–34} }
 @misc{papich_2010, title={Thoughts on testing methods for bacterial isolates}, volume={236}, number={2}, journal={Journal of the American Veterinary Medical Association}, author={Papich, M. G.}, year={2010}, pages={162–162} }
 @article{papich_2010, title={Thoughts on testing methods for bacterial isolates (On behalf of CLSI VAST subcommittee)}, volume={236}, number={2}, journal={Journal of the American Veterinary Medical Association}, author={Papich, M.G.}, year={2010}, month={Jan}, pages={162} }
 @inbook{papich_2009, place={Ames, Iowa, USA}, edition={9th}, title={ Anticonvulsant Drugs}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Papich, Mark G.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @inbook{davis_papich_heit_2009, place={Ames, Iowa, USA}, edition={9th}, title={ Antifungal and Antiviral Drugs}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Davis, Jennifer L. and Papich, Mark G. and Heit, Mark C.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @inbook{papich_2009, place={Ames, Iowa, USA}, edition={9th}, title={ Drugs Affecting Gastrointestinal Function}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Papich, Mark G.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @inbook{papich_riviere_2009, place={Ames, Iowa, USA}, edition={9th}, title={ Fluoroquinolone Antimicrobial Drugs}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Papich, Mark G. and Riviere, Jim E.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @inbook{kukanich_papich_2009, place={Ames, Iowa, USA}, edition={9th}, title={ Opioid Analgesic Drugs}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={KuKanich, Butch and Papich, Mark G.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @inbook{papich_riviere_2009, place={Ames, Iowa, USA}, edition={9th}, title={ Sulfonamides and Potentiated Sulfonamides}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Papich, Mark G. and Riviere, Jim E.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @inbook{papich_riviere_2009, place={Ames, Iowa, USA}, edition={9th}, title={Aminoglycoside Antibiotics}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Papich, Mark G. and Riviere, Jim E.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @inbook{bonagura_twedt_papich_2009, title={Appendix I, Table of Common Drugs: Approximate Dosages}, booktitle={Kirk’s Current Veterinary Therapy XIV}, publisher={Saunders- Elsevier}, year={2009}, pages={1306–1334} }
 @misc{papich_davidson_schnatz_2009, title={Appreciation for study on bromide administration in dogs}, volume={235}, number={6}, journal={Journal of the American Veterinary Medical Association}, author={Papich, M. G. and Davidson, G. and Schnatz, R. G.}, year={2009}, pages={659–659} }
 @article{papich_davidson_schnatz_2009, title={Appreciation for study on bromide administration in dogs}, volume={235}, number={6}, journal={Journal of the American Veterinary Medical Association}, author={Papich, M.G. and Davidson, G. and Schnatz, R.G.}, year={2009}, month={Sep}, pages={659} }
 @article{mathews_linder_davidson_goldman_papich_2009, title={Assessment of clotrimazole gels for in vitro stability and in vivo retention in the frontal sinus of dogs}, volume={70}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.70.5.640}, abstractNote={Abstract
Objective—To evaluate the stability and retention of viscous formulations of the antifungal drug clotrimazole in vitro and to evaluate retention times, absorption, and histologic response to these compounds when placed in the frontal sinus of dogs.
Animals—6 male Beagles.
Procedures—1% clotrimazole gels were formulated with hydroxypropyl cellulose, poloxamer, and carboxymethylcellulose sodium bases. Commercially available 1% clotrimazole creams were also evaluated. Each compound was incubated at 37°C in a funnel. Volume retained and clotrimazole stability were evaluated for 4 weeks. Six compounds were then chosen for in vivo evaluation. The frontal sinuses of 6 dogs were filled with 1 of the 6 compounds. Computed tomographic evaluation was performed weekly for up to 4 weeks to evaluate gel retention. Blood samples were collected to evaluate clotrimazole absorption. Following euthanasia, sinuses were examined histologically.
Results—Commercially available clotrimazole creams were not retained in funnels in vitro. In vivo, hydroxypropyl cellulose– and carboxymethylcellulose-based gels resulted in the most severe inflammatory response and were retained the longest. Poloxamer-based gels had a shorter retention time and were associated with less inflammation. Clotrimazole was minimally absorbed. Despite a marked inflammatory response to several of the clotrimazole-containing gels, no notable adverse clinical responses were observed.
Conclusions and Clinical Relevance—Poloxamer gels had the most promise for improving drug contact within the frontal sinus of dogs, while limiting the inflammatory response. Poloxamer gels have the additional benefit of improved handling as a result of reverse gelation (ie, they gel when warmed to 37°C).}, number={5}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Mathews, Kyle G. and Linder, Keith E. and Davidson, Gigi S. and Goldman, Rebecca B. and Papich, Mark G.}, year={2009}, month={May}, pages={640–647} }
 @inbook{papich_riviere_2009, place={Ames, Iowa, USA}, edition={9th}, title={Beta-Lactam Antibiotics: Penicillins, Cephalosporins, and Related Drugs}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Papich, Mark G. and Riviere, Jim E.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @inbook{papich_riviere_2009, place={Ames, Iowa, USA}, edition={9th}, title={Chloramphenicol and Derivatives, Macrolides, Lincosamides, and Miscellaneous Antimicrobials}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Papich, Mark G. and Riviere, Jim E.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @article{biswas_maggi_papich_keil_breitschwerdt_2009, title={Comparative Activity of Pradofloxacin, Enrofloxacin, and Azithromycin against Bartonella henselae Isolates Collected from Cats and a Human}, volume={48}, ISSN={0095-1137}, url={http://dx.doi.org/10.1128/JCM.01287-09}, DOI={10.1128/jcm.01287-09}, abstractNote={ABSTRACT
          
            Using
            Bartonella henselae
            isolates from cats and a human, the activity of pradofloxacin was compared with those of enrofloxacin and azithromycin. By Etest and disc diffusion assay, pradofloxacin showed greater antimicrobial activity than did other antibiotics. We conclude that pradofloxacin may prove useful for the treatment of
            B. henselae
            infections.
          }, number={2}, journal={Journal of Clinical Microbiology}, publisher={American Society for Microbiology}, author={Biswas, S. and Maggi, R. G. and Papich, M. G. and Keil, D. and Breitschwerdt, E. B.}, year={2009}, month={Dec}, pages={617–618} }
 @inbook{sherman_papich_2009, place={Ames, Iowa, USA}, edition={9th}, title={Drugs Affecting Animal Behavior}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Sherman, Barbara L. and Papich, Mark G.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @inbook{papich_2009, place={Ames, Iowa, USA}, edition={9th}, title={Drugs that Affect the Respiratory System}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Papich, Mark G.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @article{davis_kirk_davidson_papich_2009, title={Effects of compounding and storage conditions on stability of pergolide mesylate}, volume={234}, ISSN={["1943-569X"]}, DOI={10.2460/javma.234.3.385}, abstractNote={Abstract
Objective—To determine the effects of temperature and light over a 35-day period on stability of pergolide mesylate after compounding in an aqueous vehicle.
Design—Evaluation study.
Procedures—Pergolide was compounded into a formulation with a final target concentration of 1 mg/mL. Aliquots of the formulation were then stored at −20°, 8°, 25°, or 37°C without exposure to light or at 25°C with exposure to light for 35 days. Samples were assayed in triplicate by means of high-pressure liquid chromatography immediately after compounding and after 1, 7, 14, 21, and 35 days of storage.
Results—Mean ± SD concentration of pergolide in the formulation immediately after compounding was 1.05 ± 0.086 mg/mL. Samples exposed to light while stored at 25°C had undergone excessive degradation by day 14, samples stored at 37°C had undergone excessive degradation by day 21, and samples stored at 25°C without exposure to light had undergone excessive degradation by day 35. The decrease in expected concentration corresponded with the appearance of degradation peaks in chromatograms and with a change in color of the formulation.
Conclusions and Clinical Relevance—Results indicated that pergolide mesylate was unstable after compounding in an aqueous vehicle and that storage conditions had an effect on stability of the compounded formulation. Compounded pergolide formulations in aqueous vehicles should be stored in a dark container, protected from light, and refrigerated and should not be used > 30 days after produced. Formulations that have undergone a color change should be considered unstable and discarded.}, number={3}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Davis, Jennifer L. and Kirk, Loren Madden and Davidson, Gigi S. and Papich, Mark G.}, year={2009}, month={Feb}, pages={385–389} }
 @inbook{papich_2009, place={Ames, Iowa, USA}, edition={9th}, title={Immunosuppressive Drugs and Cyclosporine}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Papich, Mark G.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @article{biswas_maggi_papich_breitschwerdt_2009, title={Molecular mechanisms of Bartonella henselae resistance to azithromycin, pradofloxacin and enrofloxacin}, volume={65}, ISSN={0305-7453 1460-2091}, url={http://dx.doi.org/10.1093/jac/dkp459}, DOI={10.1093/jac/dkp459}, abstractNote={Sir, Bartonella henselae are fastidious, facultative intracellular bacilli that can cause bacteraemia, endocarditis, cat-scratch disease in immunocompetent patients, and bacillary angiomatosis and peliosis hepatitis in immunocompromised patients. There are a limited number of studies that have addressed the antibiotic treatment of cats infected with B. henselae. Azithromycin, a macrolide compound, has seemingly become the drug of choice to treat cats and dogs for B. henselae infection. However, relapses after antibiotic withdrawal have been reported. Azithromycin, which is derived from erythromycin, binds to the 50S subunit of the bacterial ribosome and, thus, inhibits the translation of mRNA. Fluoroquinolone antibiotics exert their antibacterial effects by inhibiting certain bacterial topoisomerase enzymes. Pradofloxacin, a third-generation fluoroquinolone, is being exclusively developed for use in veterinary medicine. Enrofloxacin is a broad-spectrum antimicrobial agent with bactericidal activity against Gram-negative and Grampositive bacteria, mycobacteria and rickettsia. As for B. henselae, potential mechanisms of resistance to azithromycin, pradofloxacin and enrofloxacin are not known. Therefore, the objective of this study was to select in vitro azithromycin-resistant, pradofloxacin-resistant and enrofloxacin-resistant mutants to determine the molecular mechanism of resistance. Six B. henselae isolates (BhH1, Mina Mia, Stray7, Bh94FO73, BhFO1946 and Bh95FO101) were used in this study. Four of these isolates (Mina Mia, Stray7, Bh94FO73 and BhFO1946) were derived from cats from the USA. BhH1 is the ATCC type strain obtained by blood culture from a febrile, HIV-infected patient in Houston, Texas. Isolate Bh95FO101 was from a sick pet cat from Israel. Pradofloxacin (5 mg) and enrofloxacin (5 mg) discs were purchased from AB Biodisk (Solna, Sweden) and supplied by Bayer HealthCare, Germany. Azithromycin (15 mg) discs were purchased from VWR International, USA. The selection of antibiotic-resistant mutants was performed by serial passages of each B. henselae isolate on blood agar plates containing an antibiotic disc. Bartonella strains were considered resistant when the inhibition zone was ,6 mm. The B. henselae azithromycin-susceptible strains and the azithromycin-resistant mutants were screened by PCR and sequencing using primers for 23S rRNA, and L4 and L22 ribosomal proteins. Strains resistant and susceptible to pradofloxacin and enrofloxacin were screened by PCR and sequencing using primers for gyrA, gyrB, parC and parE. Six B. henselae azithromycin-resistant mutants were obtained after the second in vitro passage (Table 1). Compared with the parental strain, each B. henselae azithromycin-resistant mutant had a homogenous single nucleotide substitution at position 2058 (A2058G, Escherichia coli numbering) in the 23S rRNA gene. Mutations at A2058 for certain macrolides confer the highest levels of resistance. Many independent lines of evidence indicate that adenosine 2058 is the key nucleotide involved in macrolide interaction with the bacterial ribosome. An A2058 to G transition was the first rRNA mutation shown to confer erythromycin resistance and is presently the most frequent substitution found in clinical isolates. Our in vitro results might explain relapses or treatment failures observed in vivo when using azithromycin as the sole antibiotic for treatment of Bartonella-related infections. We did not find any change in the L4 and L22 ribosomal proteins for the B. henselae azithromycinresistant mutants. All B. henselae isolates became resistant to pradofloxacin and enrofloxacin after differing numbers of subculture passages; however, in contrast to azithromycin, at least five passages}, number={3}, journal={Journal of Antimicrobial Chemotherapy}, publisher={Oxford University Press (OUP)}, author={Biswas, S. and Maggi, R. G. and Papich, M. G. and Breitschwerdt, E. B.}, year={2009}, month={Dec}, pages={581–582} }
 @article{olby_smith_humphrey_spinapolice_parke_mehta_dise_papich_2009, title={Pharmacokinetics of 4-aminopyridine derivatives in dogs}, volume={32}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2009.01072.x}, abstractNote={Blockade of potassium channels with 4‐aminopryidine (4‐AP) restores conduction to demyelinated axons and improves function. Unfortunately, 4‐AP causes adverse effects and its clinical effects are unpredictable and limited. Derivatives of 4‐AP have been tested in models of spinal cord injury in guinea pigs; three derivatives (methyl‐, ethyl‐ and t‐butyl carbamate derivatives) showed promise. This study investigates the safety and pharmacokinetics of these derivatives in dogs. Each derivative was administered orally to dogs starting at doses below effective doses in guinea pigs, and increasing the dose on sequential days. Routine blood work was performed prior to and 24 h after drug administration, blood samples were collected at intervals over 24 h after drug administration, and dogs were monitored for side effects. Derivative plasma levels were determined using high‐pressure liquid chromatography. Cerebrospinal fluid (CSF) samples were taken to determine CSF levels. No adverse effects were seen even when using doses higher than those that improved conduction in spinal cord injured guinea pigs. Peak plasma levels occurred at 36.6 (ethyl), 87 (t‐butyl) and 175 (methyl) min and plasma level was related to drug dose. Penetration of the central nervous system (CNS) was good, with CSF levels higher than plasma levels for the t‐butyl derivative.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Olby, N. J. and Smith, D. T. and Humphrey, J. and Spinapolice, K. and Parke, N. and Mehta, P. M. and Dise, D. and Papich, M.}, year={2009}, month={Oct}, pages={485–491} }
 @article{sekis_ramstead_rishniw_schwark_mcdonough_goldstein_papich_simpson_2009, title={Single-dose pharmacokinetics and genotoxicity of metronidazole in cats}, volume={11}, ISSN={["1532-2750"]}, DOI={10.1016/j.jfms.2008.06.011}, abstractNote={Single-dose pharmacokinetics and genotoxicity of metronidazole in cats were evaluated. Cats received either 5 mg/kg metronidazole intravenously, or 20 mg/kg metronidazole benzoate (12.4 mg/kg metronidazole base) orally in a single dose. Serial plasma samples were collected and assayed for metronidazole using high pressure liquid chromatography (HPLC). Genotoxicity was assessed in vitro in feline peripheral blood mononuclear cells (PBMC) and a feline T-cell lymphoma line incubated with metronidazole, and in vivo in PBMC collected before, during and 7 days after oral metronidazole, by use of the COMET assay. Systemic absorption of metronidazole was variable (mean=65±28%) with a peak of 8.84±5.4 μg/ml at 3.6±2.9 h. The terminal half-life was 5.34 h from the intravenous dose and 5.16 h from the oral dose. Systemic clearance was low (mean=91.57 ml/h/kg [1.53 ml/kg/min]), and the apparent volume of distribution (steady state) was 0.650±0.254 l/kg. Genotoxicity was detected at all concentrations of metronidazole in feline PBMC and the T-cell lymphoma line in vitro. Genotoxicity was also observed in PBMC collected from cats after 7 days of oral metronidazole but resolved within 6 days of discontinuing metronidazole.}, number={2}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Sekis, Ivana and Ramstead, Kerry and Rishniw, Mark and Schwark, Wayne S. and McDonough, Sean P. and Goldstein, Richard E. and Papich, Mark and Simpson, Kenneth W.}, year={2009}, month={Feb}, pages={60–68} }
 @article{jamadar-shroff_papich_suter_2009, title={Soy-Derived Isoflavones Inhibit the Growth of Canine Lymphoid Cell Lines}, volume={15}, ISSN={["1557-3265"]}, DOI={10.1158/1078-0432.CCR-08-1610}, abstractNote={AbstractPurpose: This study aimed to evaluate the in vitro effects of genistein, both pure genistein and a commercially available form of genistein called Genistein Combined Polysacharride (GCP), against two canine B-cell lymphoid cell lines and determine the oral bioavailability of GCP when fed to normal dogs.Experimental Design: The in vitro effect of genistein and GCP was evaluated using cell proliferation and apoptotic assays. The IC50 of both compounds was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay and propidium idodide staining. Apoptosis was evaluated using Annexin V staining, caspase 3 and 9 staining, and DNA laddering. Cell cycle analysis and Bcl-2/Bax ratios were also examined. An initial dose escalating pharmacokinetic study was used to determine if therapeutic serum levels of genistein could be reached with oral dosing of GCP in normal dogs.Results: The 72-hour in vitro IC50 of genistein and GCP against the GL-1 and 17-71 cells were both 10 μg/mL and 20 μg/mL, respectively. GCP led to cell death in both cell lines via apoptosis and treated cells exhibited increased Bax:Bcl-2 ratios. The serum concentrations of genistein in normal dogs given increasing oral doses of GCP did not reach the 72-hour in vitro IC50 in a dose escalation study.Conclusions: The results of these studies support the notion that canine high-grade B-cell lymphoma may represent a relevant large animal model of human non-Hodgkin's lymphoma to investigate the utility of GCP in chemopreventive and/or treatment strategies that may serve as a prelude to human clinical lymphoma trials.}, number={4}, journal={CLINICAL CANCER RESEARCH}, author={Jamadar-Shroff, Vahbiz and Papich, Mark G. and Suter, Steven E.}, year={2009}, month={Feb}, pages={1269–1276} }
 @misc{davis_kirk_davidson_papich_2009, title={Supports compounding standards response}, volume={234}, ISBN={0003-1488}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Davis, J. L. and Kirk, L. M. and Davidson, G. S. and Papich, M. G.}, year={2009}, pages={873–873} }
 @inbook{papich_riviere_2009, place={Ames, Iowa, USA}, edition={9th}, title={Tetracycline Antibiotics}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Papich, Mark G. and Riviere, Jim E.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @inbook{papich_2009, edition={9th}, title={Therapeutic Drug Monitoring}, booktitle={Veterinary Pharmacology & Therapeutics}, publisher={Wiley Blackwell, John Wiley & Sons}, author={Papich, Mark G.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @book{riviere_papich_2009, place={Ames, Iowa, USA}, edition={9th}, title={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, year={2009} }
 @book{riviere_papich_2009, place={Ames, Iowa, USA}, edition={9th}, title={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, year={2009} }
 @inbook{riviere_papich_2009, place={Ames, Iowa, USA}, edition={9th}, title={Veterinary Pharmacology: An Introduction to the Discipline}, booktitle={Veterinary Pharmacology and Therapeutics}, publisher={Wiley-Blackwell Publishing}, author={Riviere, Jim E. and Papich, Mark G.}, editor={Riviere, JE and Papich, MGEditors}, year={2009} }
 @article{piperisova_neel_papich_2009, title={What is your diagnosis? Marked hyperchloremia in a dog}, volume={38}, ISSN={["0275-6382"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-70350721812&partnerID=MN8TOARS}, DOI={10.1111/j.1939-165X.2009.00124.x}, abstractNote={Abstract:A 5‐year‐old neutered male Cavalier King Charles Spaniel was evaluated for a 3‐week history of progressive paresis. The dog had been receiving potassium citrate capsules to acidify urine for the past 2 years because of an earlier history of urolithiasis. Results of neurologic examination, spinal cord radiography, and magnetic resonance imaging of the skull and spinal cord revealed no lesions that could have accounted for the neurologic signs. The main abnormalities on a clinical chemistry profile were marked hyperchloremia (179 mmol/L, reference interval 108–122 mmol/L) and an anion gap of −50.4 mmol/L (reference interval 16.3–28.6 mmol/L). Because of the severe hyperchloremia, serum bromide concentration was measured (400 mg/dL; toxic concentration >150 mg/dL; some dogs may tolerate up to 300 mg/dL). Analysis of the potassium citrate capsules, which had been compounded at a local pharmacy, yielded a mean bromide concentration of 239 mg/capsule. Administration of the capsules was discontinued and there was rapid resolution of the dog's neurologic signs. This case of extreme bromide toxicity, which apparently resulted from inadvertent use of bromide instead of citrate at the pharmacy, illustrates the importance of knowing common interferents with analyte methodologies and of pursing logical additional diagnostic tests based on clinical and laboratory evidence, even when a patient's history appears to rule out a potential etiology.}, number={3}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Piperisova, Ida and Neel, Jennifer A. and Papich, Mark G.}, year={2009}, month={Sep}, pages={411–414} }
 @article{papich_2008, title={An Update on Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in Small Animals}, volume={38}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/j.cvsm.2008.09.002}, DOI={10.1016/j.cvsm.2008.09.002}, abstractNote={There are several choices of nonsteroidal anti-inflammatory drugs (NSAIDs) for treating dogs that have osteoarthritis. However, fewer drugs are available for cats. Like people, there may be greater differences among individuals in their response than there are differences among the drugs. In past practice, veterinarians often selected aspirin or phenylbutazone as an initial drug, and then progressed to off-label human drugs or other agents as an alternative. Now we have the advantage of several approved NSAIDs for which there are excellent published studies and US Food and Drug Administration or foreign approval to guide clinical use and safe dosages.}, number={6}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Papich, Mark G.}, year={2008}, month={Nov}, pages={1243–1266} }
 @misc{papich_2008, title={An update on nonsteroidal anti-Inflammatory drugs (NSAIDs) in small animals}, volume={38}, number={6}, journal={Veterinary Clinics of North America. Small Animal Practice}, author={Papich, M. G.}, year={2008}, pages={1243-} }
 @article{beddies_fox_papich_kanikanti_krebber_keene_2008, title={Comparison of the pharmacokinetic properties of bisoprolol and carvedilol in healthy dogs}, volume={69}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.69.12.1659}, abstractNote={Abstract
Objective—To compare the pharmacokinetic properties and bioavailability following oral and IV administration of bisoprolol, a second-generation β1-adrenoceptor–selective blocking agent, with those of carvedilol, a third-generation β1/β2 and α1-adrenoceptor blocking agent, in dogs.
Animals—12 healthy adult Beagles.
Procedures—A prospective, parallel group study was performed. The dogs were allocated to 1 of 2 groups (6 dogs/group) and were administered orally a 1 mg/kg dose of either bisoprolol or carvedilol. Following a 1-week washout period, each cohort received a 1 mg/kg dose of the same drug IV. Blood samples were collected before and after drug administration, and serum concentrations, pharmacokinetic variables, and bioavailability for each agent were assessed.
Results—After oral administration of bisoprolol, the geometric mean value of the area under the concentration-time curve extrapolated to infinity (AUCinf) was 2,195 μg/L (coefficient of variation [CV], 15%). After IV administration of bisoprolol, the dose-normalized geometric mean AUCinf was 2,402 μg/L (CV, 19%). Oral bioavailability of bisoprolol was 91.4%. After oral administration of carvedilol, the geometric mean AUCinf was 70 μg/L (CV, 81%). After IV administration of carvedilol, the geometric mean AUCinf was 491 μg/L (CV, 23%). Oral bioavailability of carvedilol was 14.3%. Total body clearance was low (0.42 L/h/kg) for bisoprolol and high (2.0 L/h/kg) for carvedilol.
Conclusions and Clinical Relevance—After oral administration, carvedilol underwent extensive first-pass metabolism and had limited bioavailability; bisoprolol had less first-pass effect and higher bioavailability. Collectively, these differences suggested that, in dogs, bisoprolol has less interindividual pharmacokinetic variability, compared with carvedilol.}, number={12}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Beddies, Gerald and Fox, Philip R. and Papich, Mark D. and Kanikanti, Venkata-Rangaro and Krebber, Ralph and Keene, Bruce W.}, year={2008}, month={Dec}, pages={1659–1663} }
 @article{wong_papich_davis_2008, title={Exposure to phenobarbital in a foal after nursing a mare treated with phenobarbital}, volume={22}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2007.0036.x}, abstractNote={Journal of Veterinary Internal MedicineVolume 22, Issue 1 p. 227-230 Open Access Exposure to Phenobarbital in a Foal after Nursing a Mare Treated with Phenobarbital D.M. Wong, D.M. Wong Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IASearch for more papers by this authorM.G. Papich, M.G. Papich Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorJ.L. Davis, J.L. Davis Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this author D.M. Wong, D.M. Wong Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IASearch for more papers by this authorM.G. Papich, M.G. Papich Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorJ.L. Davis, J.L. Davis Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this author First published: 14 February 2008 https://doi.org/10.1111/j.1939-1676.2007.0036.xCitations: 1 Corresponding author: Dr Wong, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011; e-mail: [email protected] AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL A7-year-old, 672-kg, pregnant Thoroughbred mare presented with a 3-week history of premature lactation and lameness. The mare was a maiden, 336 days in gestation, and had been treated with 2 doses of flunixin meglumine (1 mg/kg, PO) the day before examination. Historically, the mare had experienced intermittent seizures while in race training. A complete diagnostic investigation to determine the cause of the seizures had been performed, but the origin of seizures remained undetermined. A weak positive Western blot analysis on cerebrospinal fluid for Sarcocystis neurona was reported at that time, and the mare was treated with ponazurila (5 mg/kg PO q24h) for 30 days.1 At examination, pertinent physical examination findings included mild tachycardia (56 beats/min), sensitivity to hoof testers involving all 4 feet, and the presence of thick, purulent exudate from the left mammary gland. Rectal palpation revealed anterior presentation of a live fetus, and transrectal and transabdominal ultrasonography demonstrated areas of uteroplacental thickening (14 mm; reference interval 7.14–11.98).2 While restrained in stocks, the mare demonstrated a mild partial seizure characterized by anxiousness, muscle fasciculations of the head and neck, and ataxia. Hematologic and serum biochemical abnormalities were limited to an increased plasma fibrinogen concentration (600 mg/dL; reference interval 100–400). Lateral radiography of the feet revealed mild soft tissue swelling at the coronary band in the right front foot, suggestive of laminitis with sinking of the 3rd phalanx within the hoof. Because of laminitis and suspicion of placentitis and mastitis, the mare was administered sulfamethoxazole-trimethoprimb (30 mg/kg PO q12h for 10 days) and phenylbutazonec (3 mg/kg PO q12h for 3 days, then 1.5 mg/kg PO q12h for 3 days), the left mammary gland was milked out q8h, and supportive pads were applied to all 4 feet. Two generalized seizures were observed 14 and 16 hours after initial examination, characterized by anxiousness, generalized muscle fasciculations most prominent around the head and neck, hyperesthesia, collapse, and recumbency. At this point, treatment with phenobarbitald (5.5 mg/kg PO q12h) was initiated. Seizure activity was not subsequently noted. Uncomplicated parturition of a 42.7 kg filly occurred 3 days after admission. The filly was lethargic and hypothermic (96.4°F; reference interval 99.5–101.3), had weak peripheral pulses, and maintained a low heart rate (52–56 bpm) for 45 minutes after birth. Heart rate and temperature progressively improved over the following 90 minutes. Blood and milk samples were collected from the mare and blood was collected from the foal immediately after parturition to measure phenobarbital concentrations. Phenobarbital concentration in the mare's serum was considered therapeutic (16.3 μg/mL; reference interval 15–40).3 The concentrations of phenobarbital in the mare's milk and foal's serum were 7.5 and 12.2 μg/mL, respectively. Initial treatment for the foal included intranasal oxygen (8 L/min for 1 hour) and intravenous administration of 2 L of hyperimmunized equine plasmae and ceftiofurf (10 mg/kg q6h × 7 days). A CBC, biochemistry profile, arterial blood gas analysis, and blood cultures were submitted immediately after parturition. No substantial clinicopathologic abnormalities were noted, and amikacing (25 mg/kg IV q24h × 7 days) was subsequently administered. Bacterial growth was not observed on blood culture. An 8 × 6 inch area of thickened irregular placenta was identified in the nonpregnant horn of the placenta. This section of placenta was characterized histologically by a fibrinonecrotic exudate covering the chorion and numerous filamentous Gram-positive rods. Blood and milk samples were collected from the mare and blood was collected from the foal at various times over the next 4 days of hospitalization to measure phenobarbital concentrations. The foal remained lethargic and demonstrated decreased activity until 48 hours of age when compared with a healthy foal of similar age. The foal was encouraged or assisted to stand for the 1st 48 hours to ensure adequate milk intake and progressively nursed more aggressively and regularly over time. The mare had no further signs of seizure activity, and the mare and foal were discharged 7 days after presentation. In total, the mare was administered phenobarbital twice daily for 6 days and then once daily for 3 days until treatement was discontinued. Blood and milk samples were collected from the mare and blood from the foal 3 and 7 days after discharge. The mare and foal were reported to be doing well 1 year after discharge with no evidence of seizures. The use of any drug in lactating mares can be controversial because the amount of drug the foal is exposed to is often unknown as there are very few scientific reports on this subject in the literature. Upon administration of medications to a lactating mare, a number of factors influence exposure of the neonate to the drug via milk. These include partitioning of drug from plasma into milk, drug concentration in milk, as well as the subsequent ingestion of the drug by the neonate.4–6 Because neonatal exposure to maternally administered drugs can have detrimental effects in the infant, mathematical calculations have been validated in humans to predict the neonate's exposure to a drug.7 The milk-to-plasma (M/P) ratio represents the ratio between the drug concentration in milk and that in maternal plasma/serum.5 This ratio provides an estimate of the amount of drug to which the suckling infant is exposed. Similarly, the formula used to predict the concentration of drug in milk provides an estimate of the amount of drug in milk, taking into consideration the amount of drug that is bound to protein. The calculation of exposure index (EI) was developed in people to link the M/P ratio, milk intake, and infant drug clearance to a time-averaged drug exposure level of the suckling infant.6 The EI attempts to account for differences in drug absorption and excretion in the suckling neonate when compared with the adult and is expressed as a relationship of the foal's exposure relative to the therapeutic dose of the mother.5 Blood samples were collected from the mare via the jugular vein and milk samples were collected from the right teat into sterile tubes immediately after parturition (time 0) and at 24, 48, 73, 74, 76, 78, 80, 83, 85, 86, 88, 90, 92, 95, 97, 167 (7 days), and 263 (11 days) hours after parturition. Phenobarbital had been administered to the mare for 2 days before parturition for a total of 4 doses. Treatment was continued 2 hours after parturition (ie, phenobarbital administered at time 2, 14, 26, 38, 50 hours after parturition). Blood from the foal was collected from a cephalic vein at parturition (time 0) and at 24, 48, 72, 74, 88, 167 (7 days), and 263 (11 days) hours after parturition. Serum was harvested and milk and serum samples were analyzed on the day of collection. Phenobarbital concentrations in serum and milk were measured by fluorescence polarization immunoassay (FPIA) on an automated chemistry analyzer.h The sensitivity of the assay, as reported by the manufacturer, was 1.1 μg/mL and the precision had a coefficient of variation less than 5%. Quality control (QC) samples were analyzed before the assay at low (15 μg/mL), medium (30 μg/mL), and high (50 μg/mL) concentrations to ensure that the assay performance was within QC ranges. The concentrations of phenobarbital in the mare's serum and milk as well as the foal's serum are presented in Figure 1. Pharmacokinetic calculations were performed with computer softwarei by noncompartmental analysis. The maximum concentration (Cmax) reported was derived directly from the drug concentration versus time curves in the mare's milk and serum, as well as the foal's serum. Pertinent pharmacokinetic parameters are summarized in Table 1. The predicted amount of drug that will transfer from the plasma to the milk, known as the M/P ratio, can be calculated from the Henderson–Hasselbalch equation for acidic drugs as follows:4,8 In this equation, pHm is the pH of the mare's milk, pKa is the pKa for phenobarbital (7.3), and pHP is the pH of the mare's plasma (estimated to be 7.4).9 The pH of mare's milk has not been published. Therefore, for this report, it was estimated to be 6.49 based on an average pH of milk collected from 6 healthy mares that were < 7 days postparturition. This calculation resulted in a predicted M/P ratio of 0.51. The actual M/P ratio was then calculated from data collected in this case by the total area-under-the-curve (AUC) from an analysis of the curves presented in Figure 1. The AUC was used as it is a measure of concentration over time rather than at a single point in time, as would have been the case if Cmax were used. Therefore, AUCSerum and AUCMilk were used to calculate the value in this case. Serum drug concentrations were substituted for plasma concentrations in the calculation of the actual M/P ratio, because the FPIA method uses a serum based assay. The measured serum concentrations were corrected for protein binding because only unbound drug is transferred from mare's plasma to milk. Protein binding of phenobarbital in horses is 31%; thus, the unbound (free) fraction of drug in plasma is 0.69.10 The observed M/P AUC ratio by this analysis based on unbound concentration in plasma was 0.565, a value close to the theoretical predicted value of 0.51. Figure 1Open in figure viewerPowerPoint Phenobarbital concentrations in the serum (▪) and milk (Δ) of the mare and the serum (•) of the foal over time after administration of 5.5 mg/kg PO q12h to the mare. Arrow indicates time of parturition, black arrowhead indicates time at which phenobarbital was switched to once daily administration, gray arrowhead indicates when phenobarbital administration was discontinued. Table 1. Noncompartmental pharmacokinetic parameters of phenobarbital in the serum and milk of the mare as well as the serum of the foal calculated after administration of 5.5 mg/kg PO q12h to the mare. PharmacokineticVariable Mare'sSerum Mare'sMilk Foal'sSerum Cmax (μg/mL) 26 11.2 12.2 AUC0–∞ (hour ×μg/mL) 4480 1747 1783 λ (hour−1) 0.009 0.012 0.0124 t1/2λ (hour) 77 56 56 Cmax, maximum concentration; AUC0-∞, area under the concentration–time curve extrapolated to infinity; λ, slope of the terminal phase; t1/2λ, half-life of terminal phase. Pharmacokinetic parameters were calculated after the administration of 7 doses of phenobarbital to the mare. Once the M/P ratio has been determined, the total phenobarbital concentration in milk can be predicted to determine the dose available to be ingested by the suckling foal. Calculation of the milk drug concentration is accomplished according to the following equation:4 This calculation results in a predicted phenobarbital concentration in milk at steady state of 8.7 μg/mL. The actual observed phenobarbital concentration measured in milk fluctuated from 9 to 11.2 μg/mL between 83 and 108 hours (Fig 1). Aside from knowing the concentration of drug in milk available to the foal, the total amount of the mare's dose that the foal is exposed to per day through ingestion of milk, also known as the exposure index, can be determined. This is influenced by the amount of milk ingested by the foal and the phenobarbital clearance in the foal. To calculate the EI, the following equation was utilized6: where M/P is the milk-to-plasma concentration ratio, A is milk intake (mL/kg/min), and clearance is the foal's drug clearance as measured from other studies.11 Neonatal drug clearance for phenobarbital in foals has been reported to be 0.0564 L/kg/h (0.94 mL/kg/min).11 Assuming milk consumption of the foal to be approximately 20% of the foal's body weight12 (0.137 mL/kg/min for this foal), the predicted EI was 7.4%. However, the actual comparison of the foal's serum concentration to mare's serum concentration demonstrated an observed EI of approximately 32%. Administration of phenobarbital in pregnant women is controversial because of its potential teratogenic effects.13 Furthermore, caution must be exercised in epileptic women receiving phenobarbital while breast feeding because this drug is transferred into breast milk and demonstrates a slow elimination by nursing infants.13,14 Phenobarbital is marginally excreted into human milk because milk pH is near the drug's pKa; therefore the drug is partially ionized and protein binding is moderate (51%).5 However, low clearance of the drug by the neonate can lead to accumulation of the drug and potentially result in blood concentrations that can produce adverse effects.5,14 Potential neonatal adverse effects include sedation and decreased suckling activity resulting from cumulative concentrations of phenobarbital in the neonate.5,14 Potential deleterious effects of phenobarbital in foals include respiratory depression, bradycardia, hypotension, hypothermia, and ataxia.11,15,16 The foal presented in this report demonstrated lethargy and decreased activity during the 1st 48 hours of life, which could have been attributed to several factors, including accumulation of phenobarbital within the fetus and continued exposure to phenobarbital through mare's milk. Phenobarbital administration to the mare was hastily discontinued because we felt that the risk of seizures was low postpartum. The etiology of the seizures in the mare remains uncertain. However, seizures in people can be precipitated by stress or pain, and factors such as strenuous training, impending parturition, and pain associated with laminitis and mastitis may have contributed to the mare's seizure activity.17 With correction or treatment of these factors, we believed the likelihood of seizures was outweighed by the detrimental effects of phenobarbital on the foal. The pharmacokinetic principles presented here demonstrate that it is possible to predict phenobarbital concentration in mare's milk from theoretical values. In the mare reported here, the concentration in milk (Fig 1) was slightly higher than, but similar to, the concentration predicted from equations using the mare M/P ratio. The milk concentration from predicted equations was 8.7 μg/mL at steady state whereas the actual milk concentration measured ranged from 9 to 11.2 μg/mL. Although our calculations predicted a close approximation of drug concentration in mare's milk after treatment with phenobarbital, the exposure to the foal was notably underestimated. The actual exposure of a nursing infant to a drug is influenced by the amount ingested and the ability of the neonate to clear the drug.4,6 The exposure index is expressed as the relationship of the foal's exposure relative to the exposure to a therapeutic dose to the mother. In this case it was predicted to be only 7.4%; however, the observed EI calculated from actual foal and mare plasma phenobarbital concentrations was 32%. This discrepancy may be a result of higher oral absorption or lower clearance of the drug in this foal than previously reported values.11 Realizing the limitations of extracting information from 1 horse, the case presented here reveals preliminary information with regard to phenobarbital disposition in a lactating mare and neonatal foal. It is apparent that phenobarbital was transferred to the fetus in utero and phenobarbital is excreted into the milk and absorbed by the suckling neonatal foal. In addition, methods shown here indicate that it may be possible to predict drug concentration in milk from the mare's serum concentration, but exposure to the foal requires a more accurate estimate of the foal's drug clearance and milk consumption. In clinical cases, it is encouraged to measure both maternal and neonatal serum concentrations of phenobarbital when a mare is being treated to monitor for possible over exposure to the foal and ensure therapeutic levels in the mare. Footnotes aMarquis, Bayer HealthCare, Animal Health Division, Shawnee Mission, KS bSulfamethoxazole and trimethoprim, TEVA Pharmaceuticals, Sellersville, PA cPhenylbutazone, Phoenix Pharmaceutical, St Joseph, MO dPhenobarbital, Excellium Pharmaceutical, Fairfield, NJ eHyperimmunized Equine Plasma, MG Biologics, Ames, IA fNaxcel, Pharmacia & Upjohn, Kalamazoo, MI gAmikacin, Phoenix Pharmaceutical hAxSYM phenobarbital assay, Abbott Laboratories Diagnostic Division, Abbot Park, IL iWinNonlin version 5.1, Pharsight Corporation, Mountain View, CA Acknowledgments The authors thank Ms Delta Dise, North Carolina State University, Clinical Pharmacology Laboratory, for her assistance with drug analysis for this study. References 1 Mittel L. Seizures in the horse. Vet Clin North Am Equine Pract 1987; 3: 323– 332. 2 Bucca S, Fogarty U, Collins A, et al. Assessment of feto-placental well-being in the mare from mid-gestation to term: Transrectal and transabdominal ultrasonographic features. Theriogenology 2005; 64: 542– 557. 3 Reimer JM, Sweeney RW. Pharmacokinetics of phenobarbital after repeated oral administration in normal horses. J Vet Pharmacol Ther 1992; 15: 301– 304. 4 Atkinson HC, Begg EJ. Prediction of drug distribution into human milk from physicochemical characteristics. Clin Pharmacokinet 1990; 18: 151– 167. 5 Bar-Oz B, Nulman I, Koren G, et al. Anticonvulsants and breast feeding: A critical review. Paediatr Drugs 2000; 2: 113– 126. 6 Ito S, Lee A. Drug excretion into breast milk—Overview. Adv Drug Deliv Rev 2003; 55: 617– 627. 7 Ito S. Drug therapy for breast-feeding women. N Engl J Med 2000; 343: 118– 126. 8 Rowland M, Tozer T. Clinical Pharmacokinetics Concepts and Applications, 3rd ed. Philadelphia, PA: Williams & Wilkins; 1995: 109– 118. 9 Phenobarbital, drug profile. National library of medicine specialized information services. 2007. Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp. 10 Bailey DN. Relative binding of therapeutic drugs by sera of seven mammalian species. J Anal Toxicol 1998; 22: 587– 590. 11 Spehar AM, Hill MR, Mayhew IG, et al. Preliminary study on the pharmacokinetics of phenobarbital in the neonatal foal. Equine Vet J 1984; 16: 368– 371. 12 Koterba AM, Drummond WH. Nutritional support of the foal during intensive care. Vet Clin North Am Equine Pract 1985; 1: 35– 40. 13 Malone FD, D'Alton ME. Drugs in pregnancy: Anticonvulsants. Semin Perinatol 1997; 21: 114– 123. 14 Pote M, Kulkarni R, Agarwal M. Phenobarbital toxic levels in a nursing neonate. Indian Pediatr 2004; 41: 963– 964. 15 Wilkins P. How to use midazolam to control equine neonatal seizures. In: Proceedings American Association of Equine Practitioners. Seattle, WA: American Association of Equine Practioners; 2005: 279– 280. 16 Clement SF. Convulsive and allied syndromes of the neonatal foal. Vet Clin North Am Equine Pract 1987; 3: 333– 344. 17 Nakken KO, Solaas MH, Kjeldsen MJ, et al. Which seizure-precipitating factors do patients with epilepsy most frequently report? Epilepsy Behav 2005; 6: 85– 89. Citing Literature Volume22, Issue1January–February 2008Pages 227-230 FiguresReferencesRelatedInformation}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Wong, D. M. and Papich, M. G. and Davis, J. L.}, year={2008}, pages={227–230} }
 @misc{martinez_papich_2009, title={Factors Influencing the Gastric Residence of Dosage Forms in Dogs}, volume={98}, ISSN={["0022-3549"]}, DOI={10.1002/jps.21499}, abstractNote={An appreciation of the variables influencing canine gastric transit time is of interest both because of the push to develop pharmaceutical products that meet the therapeutic needs of the veterinary patient and because of efforts to improve our understanding of the strengths and weaknesses associated with the use of the dog as a preclinical model to support human product development. The gastric transit time of monogastric species is influenced by many factors. Physiological variables include the time of dosing relative to the phase of the interdigestive migrating myoelectric current (IMMC), the sieving properties of the pylorus, the presence or absence of food, and the inherent crushing force of the stomach. Pharmacological factors include particle size, shape and density, drug solubility, and the hardness of the tablet. Despite the importance of understanding the factors influencing gastric residence time in dogs, an in-depth examination of currently available information on this topic has not as yet been published. Therefore, this review provides an examination of each of these factors and their potential impact on canine oral drug absorption characteristics.}, number={3}, journal={JOURNAL OF PHARMACEUTICAL SCIENCES}, author={Martinez, Marilyn N. and Papich, Mark G.}, year={2009}, month={Mar}, pages={844–860} }
 @inbook{guardabassi_houser_frank_papich_2008, title={Guidelines for antimicrobial use in dogs and cats }, booktitle={Guide to Antimicrobial Use in Animals}, publisher={Blackwell Publishing, LTD}, author={Guardabassi, L. and Houser, G.A. and Frank, L.A. and Papich, M.G.}, editor={Guardabassi, L. and Jensen, L.B. and Kruse, H.Editors}, year={2008} }
 @article{bizikova_papich_olivry_2008, title={Hydroxyzine and cetirizine pharmacokinetics and pharmacodynamics after oral and intravenous administration of hydroxyzine to healthy dogs}, volume={19}, ISSN={["1365-3164"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-57449092680&partnerID=MN8TOARS}, DOI={10.1111/j.1365-3164.2008.00697.x}, abstractNote={AbstractPharmacokinetic parameters of hydroxyzine and its active metabolite cetirizine were determined after oral and intravenous administration of 2 mg kg−1 of hydroxyzine to six healthy dogs. Plasma drug levels were determined with high‐pressure liquid chromatography. Pharmacodynamic studies evaluated the suppressive effect on histamine and anticanine IgE‐mediated cutaneous wheal formation. Pharmacokinetic and pharmacodynamic correlations were determined with computer modelling. The mean systemic availability of oral hydroxyzine was 72%. Hydroxyzine was rapidly converted to cetirizine regardless of the route of administration. The mean area‐under‐the‐curve was eight and ten times higher for cetirizine than hydroxyzine after intravenous and oral dosing, respectively. After oral administration of hydroxyzine, the mean peak concentration of cetirizine was approximately 2.2 µg mL−1 and that of hydroxyzine 0.16 µg mL−1. The terminal half‐life for cetirizine varied between 10 and 11 h after intravenous and oral administration of hydroxyzine. A sigmoidal relationship was fit to the data comparing cetirizine plasma concentration to wheal suppression. Maximum inhibition (82% and 69% for histamine and anticanine IgE‐mediated skin reactions, respectively) was observed during the first 8 h, which correlated with a plasma concentration of cetirizine greater than 1.5 µg mL−1. Pharmacological modelling suggested that increasing either hydroxyzine dosages or frequencies of administration would not result in histamine inhibition superior to that obtained with twice daily hydroxyzine at 2 mg kg−1. In conclusion, there was rapid conversion of hydroxyzine to cetirizine. The reduction of wheal formation appeared almost entirely due to cetirizine. Pharmacodynamic modelling predicted that maximal antihistamine effect would occur with twice daily oral administration of hydroxyzine at 2 mg kg−1.}, number={6}, journal={VETERINARY DERMATOLOGY}, author={Bizikova, Petra and Papich, Mark G. and Olivry, Thierry}, year={2008}, month={Dec}, pages={348–357} }
 @article{guedes_papich_rude_rider_2008, title={Pharmacokinetics and physiological effects of intravenous hydromorphone in conscious dogs}, volume={31}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2008.00966.x}, abstractNote={This study evaluated the pharmacokinetics, the sedative and anti‐nociceptive effects of intravenous hydromorphone in dogs. Five adult dogs were administered hydromorphone (0.1 mg/kg and 0.2 mg/kg) and morphine (0.5 mg/kg and 1 mg/kg) at weekly intervals. Blood samples were drawn before and at 1, 2, 5, 15, 30, 60 and 120 min after drug administration. Plasma hydromorphone only was measured by high pressure liquid chromatography (HPLC) with electrochemical detection and pharmacokinetic parameters calculated. Anti‐nociceptive and sedation scores were submitted to Kruskal‐Wallis one‐way anova on ranks and post‐hoc Bonferroni test with 5% significance level. The data fitted a two‐compartment model with a fast distribution (<1 min for both doses) and slower elimination rate. Mean elimination half‐life was 80 ± 52.7 and 57.7 ± 30.4 min for the high and low dose, respectively. The apparent mean volumes of distribution at steady‐state were 7.2 ± 3 and 4.5 ± 2.4 L/kg, while the clearance was 74.7 ± 19 and 68.1 ± 20 mL/kg/min for the high and low doses, respectively. Compared to saline, hydromorphone and morphine produced significant anti‐nociception and sedation of similar magnitude for 120 min. In conclusion, intravenous hydromorphone has a large volume of distribution, and high clearance rate that exceeds hepatic blood flow. In dogs, it produced mechanical anti‐nociception and sedation of a magnitude similar to morphine.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Guedes, A. G. P. and Papich, M. G. and Rude, E. P. and Rider, M. A.}, year={2008}, month={Aug}, pages={334–343} }
 @article{arguedas_hines_papich_farnsworth_sellon_2008, title={Pharmacokinetics of Butorphanol and Evaluation of Physiologic and Behavioral Effects after Intravenous and Intramuscular Administration to Neonatal Foals}, volume={22}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2008.0200.x}, abstractNote={Background:Despite frequent clinical use, information about the pharmacokinetics (PK), clinical effects, and safety of butorphanol in foals is not available.Objectives:The purpose of this study was to determine the PK of butorphanol in neonatal foals after IV and IM administration; to determine whether administration of butorphanol results in physiologic or behavioral changes in neonatal foals; and to describe adverse effects associated with its use in neonatal foals.Animals:Six healthy mixed breed pony foals between 3 and 12 days of age were used.Methods:In a 3‐way crossover design, foals received butorphanol (IV and IM, at 0.05 mg/kg) and IV saline (control group). Butorphanol concentrations were determined by high‐performance liquid chromatography and analyzed using a noncompartmental PK model. Physiologic data were obtained at specified intervals after drug administration. Pedometers were used to evaluate locomotor activity. Behavioral data were obtained using a 2‐hour real‐time video recording.Results:The terminal half‐life of butorphanol was 2.1 hours and C0was 33.2 ± 12.1 ng/mL after IV injection. For IM injection,CmaxandTmaxwere 20.1 ± 3.5 ng/mL and 5.9 ± 2.1 minutes, respectively. Bioavailability was 66.1 ± 11.9%. There were minimal effects on vital signs. Foals that received butorphanol spent significantly more time nursing than control foals and appeared sedated.Conclusions and Clinical Importance:The disposition of butorphanol in neonatal foals differs from that in adult horses. The main behavioral effects after butorphanol administration to neonatal foals were sedation and increased feeding behavior.}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Arguedas, M. G. and Hines, M. T. and Papich, M. G. and Farnsworth, K. D. and Sellon, D. C.}, year={2008}, pages={1417–1426} }
 @article{aragon_read_gaynor_barnhart_wilson_papich_2009, title={Pharmacokinetics of an immediate and extended release oral morphine formulation utilizing the spheroidal oral drug absorption system in dogs}, volume={32}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.2008.01011.x}, DOI={10.1111/j.1365-2885.2008.01011.x}, abstractNote={This study investigated the pharmacokinetics of a human‐labeled oral morphine formulation consisting of both immediate and extended release components in dogs. In a randomized design, 14 dogs were administered either 1 or 2 mg/kg morphine orally. Blood samples were collected up to 24 h post drug administration. Plasma concentrations of morphine were measured using high‐pressure liquid chromatography with electrochemical coulometric detection. For both groups, maximal concentration occurred at 3 h post drug administration followed by a gradual decrease in morphine concentration over 24 h. There was substantial variability in morphine concentrations among dogs. The higher dose group produced a greater exposure (higher area‐under‐the‐curve), higher peak concentration, longer half‐life and a shorter time to peak concentration (tmax). The specific oral morphine formulation used in this study produced sustained plasma morphine concentrations over 24 h compared with previous intravenous dosing and immediate‐release oral morphine studies. However, the low morphine plasma concentrations and high variability produced from this formulation, suggest that the clinical application of this formulation at the doses evaluated in this study are limited.}, number={2}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Aragon, C. L. and Read, M. R. and Gaynor, J. S. and Barnhart, M. D. and Wilson, D. and Papich, M. G.}, year={2009}, month={Apr}, pages={129–136} }
 @article{wells_glerum_papich_2008, title={Pharmacokinetics of butorphanol in cats after intramuscular and buccal transmucosal administration}, volume={69}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.69.12.1548}, abstractNote={Abstract
Objective—To determine the pharmacokinetics of butorphanol in cats following IM and buccal transmucosal (BTM) administration, to determine the relative bioavailability of butorphanol following BTM administration, and to extrapolate a plasma concentration associated with antinociception on the basis of existing data from pharmacologic studies of butorphanol in cats.
Animals—6 healthy adult cats.
Procedures—Following IM or BTM butorphanol tartrate (0.4 mg/kg) administration to cats in a 2-way crossover trial, plasma samples were obtained from blood collected via a central venous catheter during a 9-hour period. Plasma butorphanol concentrations were determined by high-performance liquid chromatography.
Results—Data from 1 cat contained outliers and were excluded from pharmacokinetic analysis. Mean ± SD terminal half-life of butorphanol for the remaining 5 cats was 6.3 ± 2.8 hours and 5.2 ± 1.7 hours for IM and BTM administration, respectively. Peak plasma butorphanol concentrations were 132.0 and 34.4 ng/mL for IM and BTM administration, respectively. Time to maximal plasma concentration was 0.35 and 1.1 hours for IM and BTM administration, respectively. Extent of butorphanol absorption was 37.16% following BTM application. On the basis of data from extant pharmacologic studies of butorphanol in cats, mean ± SD duration of antinociception was 155 ± 130 minutes. The estimated plasma concentration corresponding to this time point was 45 ng/mL.
Conclusions and Clinical Relevance—In cats, IM butorphanol administration at 0.4 mg/kg maintained a plasma concentration of > 45 ng/mL for 2.7 ± 2.2 hours, whereas BTM administration at the same dose was not effective at maintaining plasma concentrations at > 45 ng/mL.}, number={12}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Wells, Sean M. and Glerum, Leigh E. and Papich, Mark G.}, year={2008}, month={Dec}, pages={1548–1554} }
 @article{sellon_papich_palmer_remund_2009, title={Pharmacokinetics of butorphanol in horses after intramuscular injection}, volume={32}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2008.01004.x}, abstractNote={A two‐way cross‐over study of the pharmacokinetics of butorphanol after intravenous and intramuscular administration at 0.08 mg/kg in six adult horses was performed. Heparinized venous blood samples were obtained prior to drug administration and at 10, 20, 30, 45, 60, 120, 180, 240, and 360 min after IV injection. Samples were obtained at the same time points and at 6 h and 12 h after IM injection. Physical examination parameters were recorded at each time point. Plasma butorphanol concentrations were determined by high performance liquid chromatography. No significant differences in any physical parameters were observed after butorphanol administration except for an increase in respiratory rate at 60 and 180 min after IV administration. Absorption of butorphanol after IM administration was very rapid (half life of absorption of 6 min) but systemic availability after IM injection was low (37%). Terminal half‐life after IV administration was much longer than half‐life after IM administration (0.57 h and 7.7 h, respectively). This difference was attributed to detection of a deep compartment after IV administration that was not detectable after IM administration. To maintain targeted plasma butorphanol concentrations above 10 ng/mL, administration of 0.08 mg/kg IM every 3 h may be necessary.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Sellon, D. C. and Papich, M. G. and Palmer, L. and Remund, B.}, year={2009}, month={Feb}, pages={62–65} }
 @article{papich_schooley_reinero_2008, title={Pharmacokinetics of cetirizine in healty cats}, volume={69}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.69.5.670}, abstractNote={Abstract
Objective—To develop a high-performance liquid chromatography (HPLC) assay for cetirizine in feline plasma and determine the pharmacokinetics of cetirizine in healthy cats after oral administration of a single dose (5 mg) of cetirizine dihydrochloride.
Animals—9 healthy cats.
Procedures—Heparinized blood samples were collected prior to and 0.5, 1, 2, 4, 6, 8, 10, and 24 hours after oral administration of 5 mg of cetirizine dihydrochloride to each cat (dosage range, 0.6 to 1.4 mg/kg). Plasma was harvested and analyzed by reverse-phase HPLC. Plasma concentrations of cetirizine were analyzed with a compartmental pharmacokinetic model. Protein binding was measured by ultrafiltration with a microcentrifugation system.
Results—No adverse effects were detected after drug administration in the cats. Mean ± SD terminal half-life was 10.06 ± 4.05 hours, and mean peak plasma concentration was 3.30 ± 1.55 μg/mL. Mean volume of distribution and clearance (per fraction absorbed) were 0.24 ± 0.09 L/kg and 0.30 ± 0.09 mL/kg/min, respectively. Mean plasma concentrations were approximately 2.0 μg/mL or higher for 10 hours and were maintained at > 0.72 μg/mL for 24 hours. Protein binding was approximately 88%.
Conclusions and Clinical Relevance—A single dose of cetirizine dihydrochloride (approx 1 mg/kg, which corresponded to approximately 0.87 mg of cetirizine base/kg) was administered orally to cats. It was tolerated well and maintained plasma concentrations higher than those considered effective in humans for 24 hours after dosing. The half-life of cetirizine in cats is compatible with once-daily dosing, and the extent of protein binding is high.}, number={5}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Papich, Mark G. and Schooley, Elizabeth K. and Reinero, Carol R.}, year={2008}, month={May}, pages={670–674} }
 @article{gilliam_streeter_papich_washburn_payton_2008, title={Pharmacokinetics of florfenicol in serum and synovial fluid after regional intravenous perfusion in the distal portion of the hind limb of adult cows}, volume={69}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.69.8.997}, abstractNote={Abstract
Objective—To define the pharmacokinetics of florfenicol in synovial fluid (SYNF) and serum from central venous (CV) and digital venous (DV) blood samples following regional IV perfusion (RIVP) of the distal portion of the hind limb in cows.
Animals—6 healthy adult cows.
Procedures—In each cow, IV catheters were placed in the dorsal common digital vein (DCDV) and the plantar vein of the lateral digit, and an indwelling catheter was placed in the metatarsophalangeal joint of the left hind limb. A pneumatic tourniquet was applied to the midmetatarsal region. Florfenicol (2.2 mg/kg) was administered into the DCDV. Samples of DV blood, SYNF, and CV (jugular) blood were collected after 0.25, 0.50, and 0.75 hours, and the tourniquet was removed; additional samples were collected at intervals for 24 hours after infusion. Florfenicol analysis was performed via high-performance liquid chromatography.
Results—In DV blood, CV blood, and SYNF, mean ± SD maximum florfenicol concentration was 714.79 ± 301.93 μg/mL, 5.90 ± 1.37 μg/mL, and 39.19 ± 29.42 μg/mL, respectively; area under the concentration versus time curve was 488.14 ± 272.53 h•μg•mL−1, 23.10 ± 6.91 h•μg•mL−1, and 113.82 ± 54.71 h•μg•mL−1, respectively; and half-life was 4.09 ± 1.93 hours, 4.77 ± 0.67 hours, and 3.81 ± 0.81 hours, respectively.
Conclusions and Clinical Relevance—Following RIVP, high florfenicol concentrations were achieved in DV blood and SYNF, whereas the CV blood concentration remained low. In cattle, RIVP of florfenicol may be useful in the treatment of infectious processes involving the distal portion of limbs.}, number={8}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Gilliam, John N. and Streeter, Robert N. and Papich, Mark G. and Washburn, Kevin E. and Payton, Mark E.}, year={2008}, month={Aug}, pages={997–1004} }
 @article{cole_papich_kwochka_hillier_smeak_lehman_2009, title={Plasma and ear tissue concentrations of enrofloxacin and its metabolite ciprofloxacin in dogs with chronic end-stage otitis externa after intravenous administration of enrofloxacin}, volume={20}, ISSN={["1365-3164"]}, DOI={10.1111/j.1365-3164.2008.00730.x}, abstractNote={AbstractThe purpose of this study was to measure the concentrations of enrofloxacin and its metabolite ciprofloxacin following intravenous administration of enrofloxacin in the plasma and ear tissue of dogs with chronic end‐stage otitis undergoing a total ear canal ablation and lateral bulla osteotomy. The goals were to determine the relationship between the dose of enrofloxacin and the concentrations of enrofloxacin and ciprofloxacin, and determine appropriate doses of enrofloxacin for treatment of chronic otitis externa and media. Thirty dogs were randomized to an enrofloxacin‐treatment group (5, 10, 15 or 20 mg kg−1) or control group (no enrofloxacin). After surgical removal, ear tissue samples (skin, vertical ear canal, horizontal ear canal, middle ear) and a blood sample were collected. Concentrations of enrofloxacin and ciprofloxacin in the plasma and ear tissue were measured by high performance liquid chromatography. Repeated measures models were applied to log‐transformed data to assess dosing trends and Pearson correlations were calculated to assess concentration associations. Ear tissue concentrations of enrofloxacin and ciprofloxacin were significantly (P < 0.05) higher than plasma concentrations. Each 5 mg kg−1increase in the dose of enrofloxacin resulted in a 72% and 37% increase in enrofloxacin and ciprofloxacin concentrations, respectively. For bacteria with an minimal inhibitory concentration of 0.12–0.15 or less, 0.19–0.24, 0.31–0.39 and 0.51–0.64 µg mL−1, enrofloxacin should be dosed at 5, 10, 15 and 20 mg kg−1, respectively. Treatment with enrofloxacin would not be recommended for a bacterial organism intermediate or resistant in susceptibility to enrofloxacin since appropriate levels of enrofloxacin would not be attained.}, number={1}, journal={VETERINARY DERMATOLOGY}, author={Cole, Lynette K. and Papich, Mark G. and Kwochka, Kenneth W. and Hillier, Andrew and Smeak, Daniel D. and Lehman, Amy M.}, year={2009}, month={Feb}, pages={51–59} }
 @book{riviere_papich_2008, title={Veterinary pharmacology and therapeutics}, volume={9th ed.}, ISBN={0813820618}, publisher={Ames, IA: Blackwell Publishing}, author={Riviere, J. E. and Papich, M.}, year={2008} }
 @article{puskar_lemons_papich_vaden_birkenheuer_2007, title={Antibiotic-resistant Corynebacterium jeikeium urinary tract infection in a cat}, volume={43}, ISSN={["0587-2871"]}, url={https://doi.org/10.5326/0430061}, DOI={10.5326/0430061}, abstractNote={A 10-year-old, castrated male, domestic longhaired cat with a history of urinary tract disease and perineal urethrostomy was presented for evaluation of persistent urinary tract inflammation. Prior to referral, diphtheroid organisms had been cultured from a urine sample obtained by cystocentesis, and they were interpreted as sample contamination. Subsequent urine culture and gene sequencing identified Corynebacterium jeikeium, which was resistant to antibiotics and appeared to be the cause of the urinary tract infection.}, number={1}, journal={JOURNAL OF THE AMERICAN ANIMAL HOSPITAL ASSOCIATION}, author={Puskar, Michelle and Lemons, Carol and Papich, Mark G. and Vaden, Shelley L. and Birkenheuer, Adam}, year={2007}, pages={61–64} }
 @inbook{papich_davis_2007, title={Antimicrobial Therapy}, ISBN={9781416024064}, url={http://dx.doi.org/10.1016/b978-1-4160-2406-4.50076-4}, DOI={10.1016/b978-1-4160-2406-4.50076-4}, booktitle={Equine Infectious Diseases}, publisher={Elsevier}, author={Papich, Mark G. and Davis, Jennifer L.}, year={2007}, pages={578–591} }
 @inbook{papich_2007, edition={Fourth}, title={Blackwell’s Five-Minute Consult Drug Formulary. Appendix IX.}, booktitle={Blackwell’s Five Minute Veterinary Consult}, publisher={Blackwell Publishing}, author={Papich, M.G.}, editor={Tilley, LP and Smith, FWK, Jr.Editors}, year={2007}, pages={1467–1531} }
 @article{guedes_papich_rude_rider_2007, title={Comparison of plasma histamine levels after intravenous administration of hydromorphone and morphine in dogs}, volume={30}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2007.00911.x}, abstractNote={This study compared plasma histamine concentrations, behavioral and cardiovascular parameters following intravenous administration of hydromorphone and morphine in conscious dogs. Five adult female dogs received a 15‐sec bolus injection of saline, hydromorphone (0.1 and 0.2 mg/kg) or morphine (0.5 and 1.0 mg/kg) randomly at weekly intervals. Blood samples were collected from the jugular vein before and at 1, 2, 5, 15, 30, 60 and 120 min after drug administration. Plasma histamine concentration, noninvasive oscillometric blood pressure, heart rate and rhythm were evaluated. Data were analyzed with repeated measures anova and Tukey–Kramer post hoc test with a 5% significance level. Median plasma histamine increased significantly only after the higher dose of morphine. Maximum plasma histamine measured was 0.8 ng/mL after saline and, after the lower and higher doses, respectively, 10.2 and 9.7 ng/mL for hydromorphone, and 440 and 589 ng/mL for morphine. One dog became hypotensive immediately after receiving the highest dose of morphine. Occasional ventricular premature contractions occurred in one dog after both opioids and dosages. No dogs vomited or defecated, but all salivated profusely with both opioids. Neuroexcitation occurred in four dogs following each opioid. In conclusion, intravenous hydromorphone induced minimal histamine release and was well tolerated by these conscious healthy dogs.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Guedes, A. G. P. and Papich, M. G. and Rude, E. P. and Rider, M. A.}, year={2007}, month={Dec}, pages={516–522} }
 @inbook{papich_2007, place={Ames, Iowa}, title={Drug Interactions }, booktitle={Lumb & Jones' Veterinary Anesthesia and Analgesia}, publisher={Blackwell Publishing}, author={Papich, M.G.}, editor={Tranquilli, W.J. and Thurmon, J.C. and Grimm, K.A.Editors}, year={2007}, pages={439–450} }
 @article{gookin_stauffer_coccaro_poore_levy_papich_2007, title={Efficacy of tinidazole for treatment of cats experimentally infected with Tritrichomonas foetus}, volume={68}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.68.10.1085}, abstractNote={Abstract
Objective—To determine the efficacy of tinidazole for treatment of cats with experimentally induced Tritrichomonas foetus infection.
Animals—8 specific-pathogen-free kittens.
Procedures—Tinidazole was tested for activity against a feline isolate of T foetus in vitro. Kittens were infected orogastrically with the same isolate and treated or not with tinidazole (30 mg/kg, PO, q 24 h for 14 days). Amoxicillin was administered 28 weeks after completion of tinidazole administration to induce diarrhea. Feces were repeatedly tested for T foetus by use of PCR assay and microbial culture for 33 weeks.
Results—Tinidazole killed T foetus at concentrations ≥ 10 μg/mL in vitro. In experimentally induced infection, tinidazole administered at 30 mg/kg decreased T foetus below the limit of molecular detection in 2 of 4 cats. Recrudescent shedding of T foetus, as elicited by amoxicillin-induced diarrhea, was diminished in cats that received prior treatment with tinidazole.
Conclusions and Clinical Relevance—Although tinidazole decreased the detection of T foetus and treated cats were resistant to later efforts to incite the infection, inability of tinidazole to eradicate infection in many cats poses a serious impediment to the drug’s effectiveness in practice.}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Gookin, Jody L. and Stauffer, Stephen H. and Coccaro, Maria R. and Poore, Matthew F. and Levy, Michael G. and Papich, Mark G.}, year={2007}, month={Oct}, pages={1085–1088} }
 @article{kukanich_huff_riviere_papich_2007, title={Naïve averaged, naïve pooled, and population pharmacokinetics of orally administered marbofloxacin in juvenile harbor seals}, volume={230}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.230.3.390}, DOI={10.2460/javma.230.3.390}, abstractNote={Abstract
Objective—To determine the pharmacokinetics of marbofloxacin after oral administration in juvenile harbor seals (Phoca vitulina) at a dose of 5 mg/kg (2.3 mg/lb) and to compare pharmacokinetic variables after pharmacokinetic analysis by naïve averaged, naïve pooled, and nonlinear mixed-effects modeling.
Design—Original study.
Animals—33 male and 22 female juvenile seals being treated for various conditions.
Procedures—Blood collection was limited to ≤ 3 samples/seal. Plasma marbofloxacin concentrations were measured via high-pressure liquid chromatography with UV detection.
Results—Mean ± SE dose of marbofloxacin administered was 5.3 ± 0.1 mg/kg (2.4 ± 0.05 mg/lb). The terminal half-life, volume of distribution (per bioavailability), and clearance (per bioavailability) were approximately 5 hours, approximately 1.4 L/kg, and approximately 3 mL/min/kg, respectively (values varied slightly with the method of calculation). Maximum plasma concentration and area under the plasma-time concentration curve were approximately 3 μg/mL and 30 h·μg/mL, respectively. Naïve averaged and naïve pooled analysis appeared to yield a better fit to the population, but nonlinear mixed-effects modeling yielded a better fit for individual seals.
Conclusions and Clinical Relevance—Values of pharmacokinetic variables were similar regardless of the analytic method used. Pharmacokinetic variability can be assessed with nonlinear mixed-effects modeling, but not with naïve averaged or naïve pooled analysis. Visual observation by experienced trainers revealed no adverse effects in treated seals. Plasma concentrations attained with a dosage of 5 mg/kg every 24 hours would be expected to be efficacious for treatment of infections caused by susceptible bacteria (excluding Pseudomonas aeruginosa).}, number={3}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={KuKanich, Butch and Huff, David and Riviere, Jim E. and Papich, Mark G.}, year={2007}, month={Feb}, pages={390–395} }
 @article{tate_blikslager_papich_2007, title={Performance of the 808-nm diode laser on equine upper airway tissue is enhanced by intravenous administration of indocyanine green}, volume={25}, ISSN={["1557-8550"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-35848961222&partnerID=MN8TOARS}, DOI={10.1089/pho.2007.2107}, abstractNote={OBJECTIVE
The objective was to develop a protocol whereby 808-nm diode laser irradiation combined with intravenous (IV) indocyanine green (ICG) could be used in non-contact mode with equal surgical efficacy to the Nd:YAG on equine tissues.


BACKGROUND DATA
The 808-nm diode laser, delivering 20-40 W of power, has been produced for veterinary medical applications. This laser's power output is less than that of most neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers. ICG is absorbed at a wavelength of 810 nm, which when concentrated in tissue should be an excellent absorber for the energy produced by the 808-nm diode laser.


METHODS
This study compares the depths and widths of thermal penetration achieved with the 808-nm diode laser in equine respiratory tissue after intravenous injection of ICG. ICG was administered at two doses: 1.5 mg/kg and 3 mg/kg. The 808-nm diode laser and Nd:YAG laser were set to deliver 200 J of energy. The depths and widths of thermal penetration obtained were compared.


RESULTS
Lesion depth and width tended to be greater in the ICG + 3 mg/kg group than in the ICG + 1.5 mg/kg group. Even so, the 1.5-mg/kg dose substantially increased the efficacy of the diode laser. Plasma ICG concentrations peaked at 5 min post-administration and then dropped markedly; lesion depth decreased after peaking at 7 min post-administration.


CONCLUSION
This study demonstrated that the 808-nm diode laser, when augmented with intravenous ICG, will be as effective a surgical tool as the Nd:YAG laser on equine upper airway tissues when applied using a non-contact fiber.}, number={5}, journal={PHOTOMEDICINE AND LASER SURGERY}, author={Tate, Lloyd P. and Blikslager, Anthony T. and Papich, Mark G.}, year={2007}, month={Oct}, pages={443–448} }
 @article{uhrig_papich_kukanich_mama_wagner_chapman_hellyer_2007, title={Pharmacokinetics and pharmacodynamics of morphine in llamas}, volume={68}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.68.1.25}, abstractNote={Abstract
Objective—To assess the pharmacokinetics and pharmacodynamics of morphine in llamas.
Animals—6 healthy adult llamas.
Procedures—Llamas received morphine sulfate in a randomized crossover design. In phase 1, they received IV or IM administration of morphine at 0.05 or 0.5 mg/kg, respectively; in phase 2, they received IV administration of morphine at 0.05, 0.25, or 0.5 mg/kg. Plasma morphine and morphine-6-glucuronide concentrations were determined by validated methods. Body temperature, heart rate, respiratory rate, sedation, and analgesia were assessed and compared with plasma concentrations by regression analysis.
Results—Total body clearance was similar between IV administration of morphine sulfate at 0.25 and 0.5 mg/kg (mean ± SD, 25.3 ± 6.9 mL/min/kg and 27.3 ± 5.9 mL/min/kg, respectively), and linearity was demonstrated between these doses. Bioavailability of morphine following IM administration at 0.5 mg/kg was 120 ± 30%. Body temperature and sedation increased as the dose of morphine administered increased. Heart rate was unaffected by varying doses. Respiratory rate decreased as dose increased. Analgesia was difficult to assess as a result of high individual variability. Intravenous administration of morphine at 0.25 mg/kg provided the most consistent increase in tolerance to electric stimulation. Pharmacodynamic modeling revealed a sigmoidal relationship between plasma concentration and sedation score.
Conclusions and Clinical Relevance—Morphine was characterized by a large apparent volume of distribution and high systemic clearance in llamas. A prolonged half-life was observed with IM injection. Intravenous administration of morphine sulfate at 0.25 mg/kg every 4 hours is suggested for further study.}, number={1}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Uhrig, Samantha R. and Papich, Mark G. and KuKanich, Butch and Mama, Khursheed R. and Wagner, Ann E. and Chapman, Phillip L. and Hellyer, Peter W.}, year={2007}, month={Jan}, pages={25–34} }
 @article{guedes_papich_rude_rider_2007, title={Pharmacokinetics and physiological effects of two intravenous infusion rates of morphine in conscious dogs}, volume={30}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2007.00849.x}, abstractNote={This study examined the pharmacokinetics and physiologic effects of two infusions rates of morphine in conscious dogs. Five adult dogs were randomly studied at weekly intervals. An initial dose of either 0.3 or 0.6 mg/kg were each followed by infusions of 0.17 and 0.34 mg/kg/h. Plasma morphine concentrations, physiological parameters, sedation and mechanical antinociception were evaluated during each infusion. Morphine was assayed by high pressure liquid chromatography (HPLC) with electrochemical coulometric detection and pharmacokinetic parameters were calculated. Data were fitted to a bi‐compartment model with a rapid distribution (<1 min for both doses) and slower termination rate. For the high and low doses, respectively, mean ± SD terminal half‐life was 38 ± 5 and 27 ± 14 min, apparent volumes of distribution at steady‐state were 1.9 ± 0.5 and 1.3 ± 0.8 L/kg, with clearances of 50 ± 15 and 67 ± 20 mL/kg/min. Steady‐state plasma concentrations ranged from 93 to 180 ng/mL and 45 to 80 ng/mL in the high and low doses, respectively. Respiratory rate increased significantly, pulse oximetry remained >95% and body temperature decreased significantly during both infusions. No vomition or neuroexcitation occurred. Sedation and mechanical antinociception were both mild during the lower infusion rate, and mild to moderate during the higher infusion rate. In conclusion, morphine pharmacokinetics was not altered by increasing infusion rates, producing stable, long‐lasting plasma concentrations.}, number={3}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Guedes, A. G. P. and Papich, M. G. and Rude, E. P. and Rider, M. A.}, year={2007}, month={Jun}, pages={224–233} }
 @article{davis_foster_papich_2007, title={Pharmacokinetics and tissue distribution of enrofloxacin and its active metabolite ciprofloxacin in calves}, volume={30}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/j.1365-2885.2007.00914.x}, DOI={10.1111/j.1365-2885.2007.00914.x}, abstractNote={The purpose of this study was to establish the pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in the plasma and interstitial fluid (ISF) following subcutaneous (s.c.) administration of enrofloxacin. Ultrafiltration probes were placed in the s.c. tissue, gluteal musculature, and pleural space of five calves. Each calf received 12.5 mg/kg of enrofloxacin. Plasma and ISF samples were collected for 48 h after drug administration and analyzed by high pressure liquid chromatography. Plasma protein binding of enrofloxacin and ciprofloxacin was measured using a microcentrifugation system. Tissue probes were well tolerated and reliably produced fluid from each site. The mean ± SD plasma half‐life was 6.8 ± 1.2 and 7.3 ± 1 h for enrofloxacin and ciprofloxacin, respectively. The combined (ciprofloxacin + enrofloxacin) peak plasma concentration (Cmax) was 1.52 μg/mL, and the combined area under the curve (AUC) was 25.33 μg/mL. The plasma free drug concentrations were 54% and 81% for enrofloxacin and ciprofloxacin, respectively, and free drug concentration in the tissue fluid was higher than in plasma. We concluded that Cmax/MIC and AUC/MIC ratios for free drug concentrations in plasma and ISF would meet suggested ratios for a targeted MIC of 0.06 μg/mL.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Davis, J. L. and Foster, D. M. and Papich, M. G.}, year={2007}, month={Dec}, pages={564–571} }
 @article{guenther-yenke_mckiernan_papich_powell_2007, title={Pharmacokinetics of an extended-release theophylline product in cats}, volume={231}, ISSN={["0003-1488"]}, DOI={10.2460/javma.231.6.900}, abstractNote={Abstract
Objective—To evaluate the pharmacokinetics of a brand of extended-release theophylline tablets and capsules in healthy cats.
Design—Randomized 3-way crossover study.
Animals—6 healthy cats.
Procedures—A single dose of aminophylline (10 mg/kg [4.5 mg/lb], IV), a 100-mg extended-release theophylline tablet, or a 125-mg extended-release theophylline capsule was administered to all cats. Plasma samples were collected via preplaced central catheters throughout a 36-hour period. Plasma samples were frozen until analyzed by use of a fluorescence polarization monoclonal immunoassay.
Results—All cats tolerated drug administration and plasma collection with no adverse effects. Peak concentrations were reached for both orally administered products between 8 and 12 hours after administration. Bioavailability was excellent. Plasma concentrations were within the human therapeutic concentration of 5 to 20 μg/mL.
Conclusions and Clinical Relevance—Daily administration of the brand of theophylline tablets and capsules used in this study at 15 mg/kg (6.8 mg/lb) and 19 mg/kg (8.6 mg/lb), respectively, maintained plasma concentrations within the desired therapeutic range in healthy cats.}, number={6}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Guenther-Yenke, Christine L. and McKiernan, Brendan C. and Papich, Mark G. and Powell, Elizabeth}, year={2007}, month={Sep}, pages={900–906} }
 @article{davis_papich_morton_gayle_blikslager_campbell_2007, title={Pharmacokinetics of etodolac in the horse following oral and intravenous administration}, volume={30}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.2007.00811.x}, DOI={10.1111/j.1365-2885.2007.00811.x}, abstractNote={The purpose of this study was to determine the pharmacokinetics of etodolac following oral and intravenous administration to six horses. Additionally,in vitrocyclooxygenase (COX) selectivity assays were performed using equine whole blood. Using a randomized two‐way crossover design, horses were administered etodolac (20 mg/kg) orally or intravenously, with a minimum 3‐week washout period. Plasma samples were collected after administration for analysis using high pressure liquid chromatography with ultraviolet detection. Following intravenous administration, etodolac had a mean plasma half‐life (t1/2) of 2.67 h, volume of distribution (Vd) of 0.29 L/kg and clearance (Cl) of 234.87 mL/h kg. Following oral administration, the average maximum plasma concentration (Cmax) was 32.57 μg/mL with at1/2of 3.02 h. Bioavailability was approximately 77.02%. Results ofin vitroCOX selectivity assays showed that etodolac was only slightly selective for COX‐2 with a COX‐1/COX‐2 selectivity ratio effective concentration (EC)50of 4.32 and for EC80of 4.77. This study showed that etodolac is well absorbed in the horse after oral administration, and may offer a useful alternative for anti‐inflammatory treatment of various conditions in the horse.}, number={1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Davis, J. L. and Papich, M. G. and Morton, A. J. and Gayle, J. and Blikslager, A. T. and Campbell, N. B.}, year={2007}, month={Feb}, pages={43–48} }
 @article{innis_papich_young_2007, title={Pharmacokinetics of metronidazole in the red-eared slider turtle (Trachemys scripta elegans) after single intracoelomic injection}, volume={30}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2007.00832.x}, abstractNote={Journal of Veterinary Pharmacology and TherapeuticsVolume 30, Issue 2 p. 168-171 Pharmacokinetics of metronidazole in the red-eared slider turtle (Trachemys scripta elegans) after single intracoelomic injection C. INNIS, C. INNIS New England Aquarium, Central Wharf, Boston, MASearch for more papers by this authorM. PAPICH, M. PAPICH College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorD. YOUNG, D. YOUNG Mount Ida College, Newton, MA, USASearch for more papers by this author C. INNIS, C. INNIS New England Aquarium, Central Wharf, Boston, MASearch for more papers by this authorM. PAPICH, M. PAPICH College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorD. YOUNG, D. YOUNG Mount Ida College, Newton, MA, USASearch for more papers by this author First published: 06 March 2007 https://doi.org/10.1111/j.1365-2885.2007.00832.xCitations: 20 Charles Innis, New England Aquarium, Central Wharf, Boston, MA 02110, USA. E-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume30, Issue2April 2007Pages 168-171 RelatedInformation}, number={2}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Innis, C. and Papich, M. and Young, D.}, year={2007}, month={Apr}, pages={168–171} }
 @book{papich_2007, place={St. Louis, Missouri}, edition={Second}, title={Saunders Handbook of Veterinary Drugs}, publisher={Saunders Elsevier}, author={Papich, M.G.}, year={2007} }
 @book{papich_2007, title={Saunders handbook of veterinary drugs. (2nd ed.)}, ISBN={1416028889}, publisher={St. Louis, Mo.: Saunders Elsevier}, author={Papich, M. G.}, year={2007} }
 @article{lennon_boyle_hutchins_friedenthal_correa_bissett_moses_papich_birkenheuer_2007, title={Use of basal serum or plasma cortisol concentrations to rule out a diagnosis of hypoadrenocorticism in dogs: 123 cases (2000-2005)}, volume={231}, ISSN={["0003-1488"]}, DOI={10.2460/javma.231.3.413}, abstractNote={Abstract
Objective—To determine whether basal serum or plasma cortisol concentration can be used as a screening test to rule out hypoadrenocorticism in dogs.
Design—Retrospective case-control study.
Animals—110 dogs with nonadrenal gland illnesses and 13 dogs with hypoadrenocorticism.
Procedures—Sensitivity and specificity of basal serum or plasma cortisol concentrations of either ≤ 1 μg/dL or ≤ 2 μg/dL to detect dogs with hypoadrenocorticism were estimated by use of the ACTH stimulation test as the gold standard.
Results—Basal cortisol concentrations of ≤ 1 μg/dL had excellent sensitivity (100%) and specificity (98.2%) for detecting dogs with hypoadrenocorticism. For basal cortisol concentrations of ≤ 2 μg/dL, sensitivity was 100% but specificity was 78.2%.
Conclusions and Clinical Relevance—On the basis of sensitivity and specificity, basal serum or plasma cortisol concentrations had high negative predictive values over a wide range of prevalence rates and can be used to rule out a diagnosis of hypoadrenocorticism. Dogs with basal cortisol concentrations > 2 μg/dL that are not receiving corticosteroids, mitotane, or ketoconazole are highly unlikely to have hypoadrenocorticism. However, if the basal cortisol concentration is ≤ 2 μg/dL, little to no information regarding adrenal gland function can be obtained and an ACTH stimulation test should be performed.}, number={3}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Lennon, Elizabeth M. and Boyle, Tonya E. and Hutchins, Rae Grace and Friedenthal, Arit and Correa, Maria T. and Bissett, Sally A. and Moses, Lorra S. and Papich, Mark G. and Birkenheuer, Adam J.}, year={2007}, month={Aug}, pages={413–416} }
 @article{tuttle_papich_wolfe_2006, title={Bone marrow hypoplasia secondary to florfenicol toxicity in a Thomson's gazelle (Gazella thomsonii)}, volume={29}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2006.00741.x}, abstractNote={Journal of Veterinary Pharmacology and TherapeuticsVolume 29, Issue 4 p. 317-319 Bone marrow hypoplasia secondary to florfenicol toxicity in a Thomson's gazelle (Gazella thomsonii) A. D. TUTTLE, A. D. TUTTLE Departments of *Clinical Sciences and †Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC; ‡North Carolina Zoological Park, Asheboro, NC, USASearch for more papers by this authorM. G. PAPICH, M. G. PAPICH Departments of *Clinical Sciences and †Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC; ‡North Carolina Zoological Park, Asheboro, NC, USASearch for more papers by this authorB. A. WOLFE, B. A. WOLFE Departments of *Clinical Sciences and †Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC; ‡North Carolina Zoological Park, Asheboro, NC, USASearch for more papers by this author A. D. TUTTLE, A. D. TUTTLE Departments of *Clinical Sciences and †Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC; ‡North Carolina Zoological Park, Asheboro, NC, USASearch for more papers by this authorM. G. PAPICH, M. G. PAPICH Departments of *Clinical Sciences and †Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC; ‡North Carolina Zoological Park, Asheboro, NC, USASearch for more papers by this authorB. A. WOLFE, B. A. WOLFE Departments of *Clinical Sciences and †Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC; ‡North Carolina Zoological Park, Asheboro, NC, USASearch for more papers by this author First published: 03 July 2006 https://doi.org/10.1111/j.1365-2885.2006.00741.xCitations: 8 Dr Allison D. Tuttle, Department of Clinical Sciences, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA. E-mail: allison_tuttle@ncsu.edu Present address: Dr Barbara A. Wolfe, The Wilds, 14000 International Road, Cumberland, OH 43732, USA. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume29, Issue4August 2006Pages 317-319 RelatedInformation}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Tuttle, AD and Papich, MG and Wolfe, BA}, year={2006}, month={Aug}, pages={317–319} }
 @inbook{papich_2006, title={Drug Therapy in Cats: Precautions and Guidelines}, ISBN={9780721604237}, url={http://dx.doi.org/10.1016/b0-72-160423-4/50034-2}, DOI={10.1016/b0-72-160423-4/50034-2}, booktitle={Consultations in Feline Internal Medicine}, publisher={Elsevier}, author={Papich, Mark G.}, year={2006}, pages={279–290} }
 @article{gookin_copple_papich_poore_stauffer_birkenheuer_twedt_levy_2006, title={Efficacy of ronidazole for treatment of feline Tritrichomonas foetus infection}, volume={20}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2006)20[536:EORFTO]2.0.CO;2}, abstractNote={Objectives: To determine the efficacy of ronidazole (RDZ), tinidazole (TDZ), and metronidazole (MDZ) against Tritrichomonas foetus in vitro and of RDZ for treatment of feline naturally occurring or experimentally induced T foetus infection. Animals: A cat naturally infected with T foetus infection and diarrhea. Ten specific-pathogen-free (SPF) kittens. Procedure: RDZ, TDZ, and MDZ were tested for activity against 3 different feline isolates of T foetus in vitro. RDZ then was administered to a naturally infected cat at 10 mg/kg PO q24h for 10 days. SPF kittens were infected orogastrically with feline T foetus and treated with either placebo or RDZ (10 mg/kg PO q12h for 14 days). Cats with relapsing infection or those receiving placebo were treated subsequently with RDZ (either 30 or 50 mg/kg PO q12h for 14 days). Feces were examined for T foetus by direct microscopy, culture, and polymerase chain reaction (PCR) testing weekly. Results: Both RDZ and TDZ killed T foetus at concentrations .0.1 mg/mL in vitro. In the naturally infected cat, RDZ abolished diarrhea and T foetus infection for 85 days after treatment, at which time infection and diarrhea relapsed. Retreatment with RDZ eradicated diarrhea and T foetus infection for over 407 days. In experimentally induced infection, RDZ at 10 mg/kg caused initial improvement, but infection relapsed in all 5 cats 2 to 20 weeks after treatment. At 30 or 50 mg/kg, 10/10 cats were negative for T foetus infection for follow-up durations of 21 to 30 weeks after treatment. Conclusions and Clinical Relevance: Oral administration of RDZ at 30 to 50 mg/kg q12h for 14 days resolved diarrhea and eradicated infection (on the basis of polymerase chain reaction [PCR] testing) in 1 naturally infected cat and 10 experimentally inoculated cats receiving a different isolate of T foetus.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Gookin, Jody L. and Copple, Christina N. and Papich, Mark G. and Poore, Matthew F. and Stauffer, Stephen H. and Birkenheuer, Adam J. and Twedt, David C. and Levy, Michael G.}, year={2006}, pages={536–543} }
 @article{sykes_ramsay_schumacher_daniel_cox_papich_2006, title={Evaluation of an implanted osmotic pump for delivery of amikacin to corn snakes (Elaphe guttata guttata)}, volume={37}, ISSN={["1937-2825"]}, DOI={10.1638/05-057-TYM-122705.1}, abstractNote={Abstract The risk of accidental envenomation to the handler of venomous snakes during drug administration limits the ability to treat these animals. One commercially available osmotic pump is a miniature self-contained cylindrical implant that operates on the basis of an osmotic pressure difference between the extracellular fluid and the osmotic agent in the pump. Osmotic pumps loaded with amikacin were surgically placed into the coelomic cavity of five adult corn snakes (Elaphe guttata guttata) (group A). Four snakes (group B) received an intramuscular injection of amikacin at 5 mg/kg followed by 2.5 mg/kg q 72 hr for a total of four injections. Plasma concentrations of amikacin were measured in both groups. Renal function was evaluated pre- and posttreatment via scintigraphy with 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) and measurement of plasma uric acid concentrations. Mean (±SD) steady state amikacin concentration for group A was 6.9 ± 1.7 μg/ml (predicted = 8.0 μg/ml), and the measured pump rate was 0.134 ± 0.017 μl/hr (predicted = 0.130 μl/hr). Mean (± SD) peak and trough plasma amikacin concentrations for group B were 22.7 ± 8.5 μg/ml and 14.3 ± 7.0 μg/ml, respectively. While neither scintigraphy nor plasma uric acid concentrations indicated toxicity in either group, continuous administration of aminoglycosides may cause nephrotoxicity, and it is unknown whether this delivery method of amikacin would be efficacious in treating bacterial infections in snakes. In addition, due to migration of one pump into the trachea causing asphyxiation and death, these pumps may not be appropriate for intracoelomic placement in corn snakes. Nonetheless, the pumps delivered the drug at a predictable rate and were efficacious in achieving a constant plasma concentration of amikacin at the predicted level. Osmotic pumps may offer a safer alternative to periodic intramuscular injections for drug delivery in venomous or aggressive snakes.}, number={3}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Sykes, John M. and Ramsay, Edward C. and Schumacher, Juergen and Daniel, Gregory B. and Cox, Sherry and Papich, Mark}, year={2006}, month={Sep}, pages={373–380} }
 @article{davis_little_blikslager_papich_2006, title={Mucosal permeability of water-soluble drugs in the equine jejunum: a preliminary investigation}, volume={29}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.2006.00757.x}, DOI={10.1111/j.1365-2885.2006.00757.x}, abstractNote={Ussing chambers have been used to study the mucosal permeability of drugs in humans, rats and other species. This data can then be used to developin vitro/in vivocorrelations (IVIVC) for drugs based on the Biopharmaceutics Classification System (BCS). Due to the poor oral bioavailability of many drugs in the horse, this method may be useful for screening drugs before development to determine if they warrant further study. Cephalexin (CPX), marbofloxacin (MAR), metronidazole (MTZ) and fluconazole (FCZ) were chosen for this study based on the wide range of physicochemical properties and bioavailability in the horse. Permeability was ranked as follows: MTZ > FCZ > MAR > CPX. This correlated with the bioavailability (R2 = 0.633447), the Log P (R2 = 0.648517), as well as the molecular weight (R2 = 0.851208) of the drugs. Metronidazole induced a decrease in the tissue transepithelial resistance, suggestive of the possibility of tissue toxicity, which may have falsely increased its permeability. The low permeability of cephalexin across the tissue may indicate a lack of active transporters that are found in other species. From this study, we can conclude that the Ussing chamber is a promising method for determining mucosal permeability in the horse.}, number={5}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Davis, J. L. and Little, D. and Blikslager, A. T. and Papich, M. G.}, year={2006}, month={Oct}, pages={379–385} }
 @article{davis_salmon_papich_2006, title={Pharmacokinetics and tissue distribution of doxycycline after oral administration of single and multiple doses in horses}, volume={67}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.67.2.310}, abstractNote={Abstract
Objective—To determine pharmacokinetics, safety, and penetration into interstitial fluid (ISF), polymorphonuclear leukocytes (PMNLs), and aqueous humor of doxycycline after oral administration of single and multiple doses in horses.
Animals—6 adult horses.
Procedure—The effect of feeding on drug absorption was determined. Plasma samples were obtained after administration of single or multiple doses of doxycycline (20 mg/kg) via nasogastric tube. Additionally, ISF, PMNLs, and aqueous humor samples were obtained after the final administration. Horses were monitored for adverse reactions.
Results—Feeding decreased drug absorption. After multiple doses, mean ± SD time to maximum concentration was 1.63 ± 1.36 hours, maximum concentration was 1.74 ± 0.3 μg/mL, and elimination half-life was 12.07 ± 3.17 hours. Plasma protein binding was 81.76 ± 2.43%. The ISF concentrations correlated with the calculated percentage of non-protein-bound drug. Maximum concentration was 17.27 ± 8.98 times as great in PMNLs, compared with plasma. Drug was detected in aqueous humor at 7.5% to 10% of plasma concentrations. One horse developed signs of acute colitis and required euthanasia.
Conclusions and Clinical Relevance—Results suggest that doxycycline administered at a dosage of 20 mg/kg, PO, every 24 hours will result in drug concentrations adequate for killing intracellular bacteria and bacteria with minimum inhibitory concentration ≤ 0.25 μg/mL. For bacteria with minimum inhibitory concentration of 0.5 to 1.0 μg/mL, a dosage of 20 mg/kg, PO, every 12 hours may be required; extreme caution should be exercised with the higher dosage until more safety data are available.}, number={2}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Davis, JL and Salmon, JH and Papich, MG}, year={2006}, month={Feb}, pages={310–316} }
 @article{zimmerman_armstrong_curro_dankoff_vires_cook_jaros_papich_2006, title={Pharmacokinetics of florfenicol after a single intramuscular dose in white-spotted bamboo sharks (Chiloscyllium plagiosum)}, volume={37}, ISSN={["1042-7260"]}, DOI={10.1638/05-065.1}, abstractNote={Abstract This study evaluated the pharmacokinetics of florfenicol in the white-spotted bamboo shark (Chiloscyllium plagiosum). In addition to the pharmacokinetics, the potential application for treatment of bacterial meningitis was explored. A pilot study was used to compare doses of 30, 40, and 50 mg/kg i.m. Following that study, 10 adult sharks were administered a single i.m. dose of florfenicol at 40 mg/kg. Plasma and cerebrospinal fluid were collected and analyzed for florfenicol by a sensitive and specific high-pressure liquid chromatographic method. Pharmacokinetic analysis was performed using both non-compartmental and compartmental techniques. The absorption produced an average peak at 54 (±19) hr from the i.m. site of administration, and the half-life was prolonged, averaging 269.79 hr (±135.87). Florfenicol plasma concentrations peaked at an average of 11.85 μg/ml (±1.45) and were maintained above our target minimum inhibitory concentration of 4–8 μg/ml for at least 120 hr. Cerebrospinal fluid concentrations peaked at an estimated 9 μg/ml around 48 hr, surpassing the target minimum inhibitory concentration for at least 72 hr.}, number={2}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Zimmerman, DM and Armstrong, DL and Curro, TG and Dankoff, SM and Vires, KW and Cook, KK and Jaros, ND and Papich, MG}, year={2006}, month={Jun}, pages={165–173} }
 @article{flammer_papich_2006, title={Pharmacokinetics of fluconazole after oral administration of single and multiple doses in African grey parrots}, volume={67}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.67.3.417}, abstractNote={Abstract
Objective—To determine the pharmacokinetics and effects of orally administered fluconazole in African grey parrots.
Animals—40 clinically normal Timneh African grey parrots (Psittacus erithacus timneh).
Procedure—In single-dose trials, parrots were placed into groups of 4 to 5 birds each and fluconazole was administered orally at 10 and 20 mg/kg. Blood samples for determination of plasma fluconazole concentrations were collected from each group at 2 or 3 of the following time points: 1, 3, 6, 9, 12, 24, 31, 48, and 72 hours. In multiple-dose trials, fluconazole was administered orally to groups of 5 birds each at doses of 10 and 20 mg/kg every 48 hours for 12 days. Trough plasma concentrations were measured 3 times during treatment. Groups receiving 20 mg/kg were monitored for changes in plasma biochemical analytes, and blood samples were collected on days 1 and 13 of treatment to allow comparison of terminal half-life.
Results—Peak plasma concentrations of fluconazole were 7.45 and 18.59 μg/mL, and elimination half-lives were 9.22 and 10.19 hours for oral administration of 10 and 20 mg/kg, respectively. Oral administration of fluconazole for 12 days at 10 or 20 mg/kg every 48 hours did not cause identifiable adverse effects or change the disposition of fluconazole.
Conclusions and Clinical Relevance—Oral administration of fluconazole to parrots at 10 to 20 mg/kg every 24 to 48 hours maintains plasma concentrations above the minimum inhibitory concentration for several common yeast species. The prolonged dosing interval is an advantage of this treatment regimen.}, number={3}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Flammer, K and Papich, M}, year={2006}, month={Mar}, pages={417–422} }
 @article{tuttle_papich_lewbart_christian_gunkel_harms_2006, title={Pharmacokinetics of ketoprofen in the green iguana (Iguana iguana) following single intravenous and intramuscular injections}, volume={37}, ISSN={["1937-2825"]}, DOI={10.1638/06-029.1}, abstractNote={Abstract The nonsteroidal antiinflammatory drug ketoprofen (KTP) is a commonly used antiinflammatory and analgesic agent in reptile medicine, but no studies documenting its pharmacokinetics in this species have been published. Ketoprofen was administered as a racemic mixture to green iguanas (Iguana iguana) intravenously (i.v.) and intramuscularly (i.m.) at 2 mg/kg. Pharmacokinetic analyses were performed and indicated that ketoprofen in iguanas administered by the intravenous route has a classical two-compartmental distribution pattern, a slow clearance (67 ml/ kg/hr) and a long terminal half-life (31 hr) compared to ketoprofen studies reported in mammals. When delivered by the intramuscular route, bioavailability was 78%. These data indicate the daily dosing that is generally recommended for reptile patients, as an extrapolation from mammalian data, may be more frequent than necessary.}, number={4}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Tuttle, Allison D. and Papich, Mark and Lewbart, Gregory A. and Christian, Shane and Gunkel, Conny and Harms, Craig A.}, year={2006}, month={Dec}, pages={567–570} }
 @article{davis_salmon_papich_2006, title={Pharmacokinetics of voriconazole after oral and intravenous administration to horses}, volume={67}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.67.6.1070}, abstractNote={Abstract
Objective—To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution.
Animals—6 adult horses.
Procedures—Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed.
Results—Voriconazole was adequately absorbed after oral administration in horses, with a systemic bioavailability of 135.75 ± 18.41%. The elimination half-life after a single orally administered dose was 13.11 ± 2.85 hours, and the maximum plasma concentration was 2.43 ± 0.4 μg/mL. Plasma protein binding was 31.68%, and the octanol:water partition coefficient was 64.69. No adverse reactions were detected during the study.
Conclusions and Clinical Relevance—Voriconazole has excellent absorption after oral administration and a long half-life in horses. On the basis of the results of this study, it was concluded that administration of voriconazole at a dosage of 4 mg/kg, PO, every 24 hours will attain plasma concentrations adequate for treatment of horses with fungal infections for which the fungi have a minimum inhibitory concentration ≤ 1 μg/mL. Because of the possible nonlinearity of this drug as well as the potential for accumulation, chronic dosing studies and clinical trials are needed to determine the appropriate dosing regimen for voriconazole in horses.}, number={6}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Davis, JL and Salmon, JH and Papich, MG}, year={2006}, month={Jun}, pages={1070–1075} }
 @article{gandolf_papich_bringardner_atkinson_2006, title={Single-dose intravenous and oral pharmacokinetics of enrofloxacin in goral (Nemorrhaedus goral arnouxianus)}, volume={37}, ISSN={["1042-7260"]}, DOI={10.1638/05-015.1}, abstractNote={Abstract This study describes the pharmacokinetics of enrofloxacin following oral and i.v. administration to goral (Nemorrhaedus goral arnouxianus). The objective of this study was to expand upon current antimicrobial treatment options available for use in goral by measuring plasma concentrations and examining the pharmacokinetics of enrofloxacin in these animals. Two single-dose treatments of enrofloxacin were administered to four goral in a crossover design. Single-dose treatments consisted of administration of injectable enrofloxacin i.v. (5 mg/kg) and enrofloxacin tablets (136 mg chewable tablets) dissolved in a grain slurry and administered p.o. (10 mg/kg). Plasma levels of enrofloxacin and its metabolite ciprofloxacin were measured with the use of high-performance liquid chromatography with UV detection. Plasma volume of distribution for i.v. enrofloxacin was 2.15 ± 1.01 L/kg, with a mean elimination half-life of 13.3 hr and total body clearance of 0.19 ± 0.14 L/kg/hr. The maximum plasma concentration measured for oral enrofloxacin was 2.77 μg/ml, with a mean half-life of 5.2 hr and systemic availability of 14.6%. The area under the plasma concentration over time curve (AUC) for oral enrofloxacin was 21.06 μg/hr/ml. The area under the plasma concentration over time curve generated for oral enrofloxacin in goral yields an area under the plasma concentration over time curve to minimum inhibitory concentration ratio > 100 for many gram-positive and gram-negative bacterial pathogens common to small ruminants. Based on these results, oral enrofloxacin may be considered for further study as a treatment option for susceptible infections in goral.}, number={2}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Gandolf, AR and Papich, MG and Bringardner, AB and Atkinson, MW}, year={2006}, month={Jun}, pages={145–150} }
 @article{davis_papich_weingarten_2006, title={The pharmacokinetics of orbifloxacin in the horse following oral and intravenous administration}, volume={29}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2006.00737.x}, abstractNote={The purpose of this study was to determine the pharmacokinetics and physicochemical characteristics of orbifloxacin in the horse. Six healthy adult horses were administered oral and intravenous orbifloxacin at a dose of 2.5 mg/kg. Plasma samples were collected and analyzed by high‐pressure liquid chromatography with ultraviolet detection. Plasma protein binding and lipophilicity were determinedin vitro. Following i.v. administration, orbifloxacin had a terminal half‐life (t1/2) of 5.08 h and a volume of distribution (Vd(ss)) of 1.58 L/kg. Following oral administration, the average maximum plasma concentration (Cmax) was 1.25 μg/mL with at1/2of 3.42 h. Systemic bioavailability was 68.35%. Plasma protein binding was 20.64%. The octanol:water partition coefficient (pH 7.4) was 0.2 ± 0.11. No adverse reactions were noted during this study. Dosage regimens were determined from the pharmacokinetic–pharmacodynamic parameters established for fluoroquinolone antibiotics. For susceptible bacteria, an oral dose of approximately 5 mg/kg once daily will produce plasma concentrations within the suggested range. This dose is suggested for further studies on the clinical efficacy of orbifloxacin for treatment of susceptible bacterial infections in the horse.}, number={3}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Davis, JL and Papich, MG and Weingarten, A}, year={2006}, month={Jun}, pages={191–197} }
 @inbook{papich_bidgood_2005, place={St. Louis, Missouri}, edition={6th}, title={Antimicrobial Drug Therapy}, booktitle={Textbook of Veterinary Internal Medicine: Diseases of the Dog and Cat}, publisher={Elsevier Saunders}, author={Papich, MG and Bidgood, T}, editor={Ettinger, S.J. and Feldman, E.C.Editors}, year={2005}, pages={498–502} }
 @article{morley_apley_besser_burney_fedorka-cray_papich_traub-dargatz_weese_2005, title={Antimicrobial drug use in veterinary medicine}, volume={19}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2005)19[617:ADUIVM]2.0.CO;2}, abstractNote={Recognizing the importance of antimicrobial resistance and the need for veterinarians to aid in efforts for maintaining the usefulness of antimicrobial drugs in animals and humans, the Board of Regents of the American College of Veterinary Internal Medicine charged a special committee with responsibility for drafting this position statement regarding antimicrobial drug use in veterinary medicine. The Committee believes that veterinarians are obligated to balance the well-being of animals under their care with the protection of other animals and public health. Therefore, if an animal's medical condition can be reasonably expected to improve as a result of treatment with antimicrobial drugs, and the animal is under a veterinarian's care with an appropriate veterinarian-client-patient relationship, veterinarians have an obligation to offer antimicrobial treatment as a therapeutic option. Veterinarians also have an obligation to actively promote disease prevention efforts, to treat as conservatively as possible, and to explain the potential consequences associated with antimicrobial treatment to animal owners and managers, including the possibility of promoting selection of resistant bacteria. However, the consequences of losing usefulness of an antimicrobial drug that is used as a last resort in humans or animals with resistant bacterial infections might be unacceptable from a public or population health perspective. Veterinarians could therefore face the difficult choice of treating animals with a drug that is less likely to be successful, possibly resulting in prolonged or exacerbated morbidity, to protect the good of society. The Committee recommends that voluntary actions be taken by the veterinary profession to promote conservative use of antimicrobial drugs to minimize the potential adverse effects on animal or human health. The veterinary profession must work to educate all veterinarians about issues related to conservative antimicrobial drug use and antimicrobial resistance so that each individual is better able to balance ethical obligations regarding the perceived benefit to their patients versus the perceived risk to public health. Specific means by which the veterinary profession can promote stewardship of this valuable resource are presented and discussed in this document.}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Morley, PS and Apley, MD and Besser, TE and Burney, DP and Fedorka-Cray, PJ and Papich, MG and Traub-Dargatz, JL and Weese, JS}, year={2005}, pages={617–629} }
 @article{kukanich_lascelles_papich_2005, title={Assessment of a von Frey device for evaluation of the antinociceptive effects of morphine and its application in pharmacodynamic modeling of morphine in dogs}, volume={66}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2005.66.1616}, DOI={10.2460/ajvr.2005.66.1616}, abstractNote={AbstractObjective—To assess the use of a von Frey device as a mechanical nociceptive stimulus for evaluation of the antinociceptive effects of morphine in dogs and its potential application in the pharmacodynamic modeling of morphine in that species.Animals—6 healthy Beagles.Procedure—von Frey thresholds were measured in all dogs before and at intervals after they received no treatment (control dogs) and IV administration of morphine sulfate (1 mg/kg; treated dogs) in a crossover study. The von Frey device consisted of a rigid tip (0.5 mm in diameter) and an electronic load cell; the operator was unaware of recorded measurements.Results—Application of the von Frey device was simple and well tolerated by all dogs and caused no apparent tissue damage. No significant changes in thresholds were detected in the control dogs at 8 hourly measurements, indicating a lack of acquired tolerance, learned aversion, or local hyperalgesia. When assessed as a group, treated dogs had significantly high thresholds for 4 hours following morphine administration, compared with baseline values; individually, thresholds decreased to baseline values within (mean ± SE) 2.8 ± 0.6 hours. The maximal effect (change from baseline values) was 213 ± 43%, and the plasma morphine concentration to achieve 50% maximal effect was 13.92 ± 2.39 ng/mL.Conclusions and Clinical Relevance—Data suggest that, in dogs, evaluation of the antinociceptive effect and pharmacodynamic modeling of a dose of morphine sulfate (1 mg/kg, IV) can be successfully achieved by use of a von Frey device. (Am J Vet Res2005;66:1616–1622)}, number={9}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={KuKanich, Butch and Lascelles, B. Duncan X. and Papich, Mark G.}, year={2005}, month={Sep}, pages={1616–1622} }
 @article{flammer_papich_2005, title={Assessment of plasma concentrations and effects of injectable doxycycline in three psittacine species}, volume={19}, ISSN={["1938-2871"]}, DOI={10.1647/2004-007.1}, abstractNote={Abstract The disposition and effects of 2 formulations of injectable doxycycline administered at 100 mg/kg were investigated to determine if plasma concentrations considered adequate for treating avian chlamydiosis (1 μg/ml) could be safely maintained in 3 species of psittacine birds. Five orange-winged Amazon parrots (Amazona amazonica) that received a commercial doxycycline hyclate formulation (20 mg/ml) intramuscularly achieved maximum plasma doxycycline concentrations of 9.33 ± 0.82 μg/ml and maintained concentrations >1 μg/ml for 5 days. In a second trial, 8 orange-winged Amazon parrots and 8 Goffin's cockatoos (Cacatua goffini) received micronized pharmacist-compounded doxycycline (75 mg/ml IM). In orange-winged Amazon parrots, maximum plasma doxycycline concentration was 2.54 ± 0.38 μg/ml, and concentrations of approximately 0.5 μg/ml were sustained from 24–168 hours. In Goffin's cockatoos, maximum plasma doxycycline concentration was 3.49 ± 0.18 μg/ml, and concentrations >1 μg/ml were maintained for at least 168 hours. In a third trial, groups (n = 4) of orange-winged Amazon parrots, Goffin's cockatoos, and timneh African grey parrots (Psittacus erithacus timneh) received micronized pharmacist-compounded doxycycline (100 mg/ml IM); a separate group of timneh African grey parrots (n = 4) received the same dose subcutaneously. Plasma doxycycline concentrations were lower than in the second trial, and no group achieved 1 μg/ml. After 24 hours, concentrations were sustained at approximately 0.4–0.8 μg/ml in Goffin's cockatoos and at 0.3–0.4 μg/ml in orange-winged Amazon parrots and timneh African grey parrots for at least 20 days. No significant difference was found in doxycycline plasma concentrations in timneh African grey parrots injected subcutaneously as compared with those in parrots injected intramuscularly. Reaction at the injection site was observed in all birds receiving pharmacist-compounded doxycycline, including marked, persistent swelling at the intramuscular injection site and sloughing of skin and scab formation at subcutaneous injection sites. The results of this study show that both the efficacy and the severity of injection-site reactions seen with use of this particular formulation of pharmacist-compounded doxycycline may vary depending on the species treated and particular drug batch.}, number={3}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Flammer, K and Papich, M}, year={2005}, month={Sep}, pages={216–224} }
 @misc{papich_2005, title={Drug compounding for veterinary patients}, volume={7}, number={2}, journal={AAPS Journal}, author={Papich, M. G.}, year={2005} }
 @article{papich_2005, title={Drug compounding for veterinary patients}, volume={7}, number={2}, journal={AAPS Journal (American Association of Pharmaceutical Scientists)}, author={Papich, M.G.}, year={2005}, month={Sep}, pages={E281–287} }
 @article{gore_harms_kukanich_forsythe_lewbart_papich_2005, title={Enrofloxacin pharmacokinetics in the European cuttlefish, Sepia officinalis, after a single i.v. injection and bath administration}, volume={28}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2005.00684.x}, abstractNote={Enrofloxacin pharmacokinetics were studied in European cuttlefish, Sepia officinalis, after a single 5 mg/kg i.v. injection or a 2.5 mg/L 5 h bath. A pilot study with two animals was also performed following a 10 mg/kg p.o. administration. The concentration of enrofloxacin in hemolymph was assayed using high‐performance liquid chromatography (HPLC) and pharmacokinetic parameters were derived from compartmental methods. In the i.v. study, the terminal half‐life (t1/2), apparent volume of distribution, and systemic clearance were respectively 1.81 h, 385 mL/kg, and 4.71 mL/min/kg. Following bath administration the t1/2, peak hemolymph concentration (Cmax), and area under the curve to infinity (AUC0−∞) were 1.01 h, 0.5 ± 0.12 μg/mL, and 0.98 μg·h/mL, respectively. After oral administration, the t1/2, Cmax, and AUC0−∞ were 1.01 h, 10.95 μg/mL, 26.71 μg·h/mL, respectively. The active metabolite of enrofloxacin, ciprofloxacin, was not detected in any samples tested. The hemolymph concentration was still above minimum inhibitory concentration (MIC) values for shrimp and fish bacterial isolates at 6 h after i.v. administration, therefore, a dose of 5 mg/kg i.v. every 8–12 h is suggested for additional studies of efficacy. The Cmax value for the water bath was lower than for the i.v. study, but a bath of 2.5 mg/L for 5 h once to twice daily is suggested for additional studies to test efficacy against highly susceptible organisms. Although only two animals were used for the oral study, a dose of 10 mg/kg produced hemolymph concentrations of enrofloxacin that were in a range consistent with therapeutic efficacy in other species.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Gore, SR and Harms, CA and Kukanich, B and Forsythe, J and Lewbart, GA and Papich, MG}, year={2005}, month={Oct}, pages={433–439} }
 @article{lewbart_butkus_papich_coleman_krum_noga_2005, title={Evaluation of a method of intracoelomic catheterization in koi}, volume={226}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.2005.226.784}, DOI={10.2460/javma.2005.226.784}, abstractNote={AbstractObjective—To develop an easy and safe method for catheterization and determine the pharmacokinetics of a single dose of enrofloxacin after intracoelomic administration in koi.Design—Prospective study.Animals—20 healthy koi.Procedure—6 koi were anesthetized with tricaine methanesulfonate, and a 23-gauge, three-fourths-inch butterfly catheter was inserted into the coelomic cavity and secured. Catheters were flushed daily for 6 days with 0.4 mL of sterile saline (0.9% NaCl) solution containing heparin (100 units of heparin in 250 mL of saline solution) without removing koi from the aquarium. At the end of the sixth day (144 hours), each of the 6 catheterized koi and 6 uncatheterized (control) koi was anesthetized individually. Enrofloxacin (10 mg/kg [4.5 mg/lb]) was administered to catheterized koi via the injection port and to control koi via a 23-gauge needle in the same site as the catheter placement. A pharmacokinetics study was performed on multiple plasma samples to validate the efficiency of the catheter. Reliability of the catheterization method was determined in 8 koi.Results—All 6 catheters remained patent and effective for the 6 days prior to the start of the pharmacokinetics study. Results for the 2 routes of administration were comparable, and all koi survived the study without any detectable clinical problems.Conclusions and Clinical Relevance—An intracoelomic catheter was effective and safe when maintained in koi for at least 6 days. This would be highly beneficial for veterinarians, clients, and fish, especially when intracoelomic administration of a drug would require daily or more frequent dosing. (J Am Vet Med Assoc2005;226: 784–788)}, number={5}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Lewbart, Gregory A. and Butkus, Deborah A. and Papich, Mark G. and Coleman, Angela K. and Krum, Howard N. and Noga, Edward J.}, year={2005}, month={Mar}, pages={784–788} }
 @article{bennett_papich_hoenig_fettman_lappin_2005, title={Evaluation of transdermal application of glipizide in a pluronic lecithin gel to healthy cats}, volume={66}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2005.66.581}, abstractNote={AbstractObjective—To evaluate plasma glipizide concentration and its relationship to plasma glucose and serum insulin concentrations in healthy cats administered glipizide orally or transdermally.Animals—15 healthy adult laboratory-raised cats.Procedure—Cats were randomly assigned to 2 treatment groups (5 mg of glipizide, PO or transdermally) and a control group. Blood samples were collected 0, 10, 20, 30, 45, 60, 90, and 120 minutes and 4, 6, 10, 14, 18, and 24 hours after administration to determine concentrations of insulin, glucose, and glipizide.Results—Glipizide was detected in all treated cats. Mean ± SD transdermal absorption was 20 ± 14% of oral absorption. Mean maximum glipizide concentration was reached 5.0 ± 3.5 hours after oral and 16.0 ± 4.5 hours after transdermal administration. Elimination half-life was variable (16.8 ± 12 hours orally and 15.5 ± 15.3 hours transdermally). Plasma glucose concentrations decreased in all treated cats, compared with concentrations in control cats. Plasma glucose concentrations were significantly lower 2 to 6 hours after oral administration, compared with after transdermal application; concentrations were similar between treatment groups and significantly lower than for control cats 10 to 24 hours after treatment.Conclusions and Clinical Relevance—Transdermal absorption of glipizide was low and inconsistent, but analysis of our results indicated that it did affect plasma glucose concentrations. Transdermal administration of glipizide is not equivalent to oral administration. Formulation, absorption, and stability studies are required before clinical analysis can be performed. Transdermal administration of glipizide cannot be recommended for clinical use at this time. (Am J Vet Res2005;66:581–588)}, number={4}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Bennett, N and Papich, MG and Hoenig, M and Fettman, MJ and Lappin, MR}, year={2005}, month={Apr}, pages={581–588} }
 @article{gandolf_papich_bringardner_atkinson_2005, title={Pharmacokinetics after intravenous, subcutaneous, and oral administration of enrofloxacin to alpacas}, volume={66}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2005.66.767}, DOI={10.2460/ajvr.2005.66.767}, abstractNote={AbstractObjective—To determine plasma concentrations of enrofloxacin and the active metabolite ciprofloxacin after PO, SC, and IV administration of enrofloxacin to alpacas.Animals—6 adult female alpacas.Procedure—A crossover design was used for administration of 3 single-dose treatments of enrofloxacin to alpacas, which was followed by an observational 14-day multiple-dose regimen. Single-dose treatments consisted of IV and SC administration of injectable enrofloxacin (5 mg/kg) and PO administration of enrofloxacin tablets (10 mg/kg) dissolved in grain to form a slurry. Plasma enrofloxacin concentrations were measured by use of high-performance liquid chromatography. The multiple-dose regimen consisted of feeding a mixture of crushed and moistened enrofloxacin tablets mixed with grain. Behavior, appetite, and fecal quality were monitored throughout the 14-day treatment regimen and for 71 additional days following treatment.Results—Mean half-life following IV, SC, and PO administration was 11.2, 8.7, and 16.1 hours, respectively. For SC and PO administration, mean total systemic availability was 90.18% and 29.31%, respectively; mean maximum plasma concentration was 3.79 and 1.81 µg/mL, respectively; and area under the curve (AUC) was 50.05 and 33.97 (µg × h)/mL, respectively. The SC or PO administration of a single dose of enrofloxacin yielded a ratio for AUC to minimum inhibitory concentration > 100 for many grampositive and gram-negative bacterial pathogens common to camelids.Conclusions and Clinical Relevance—The administration of enrofloxacin (5 mg/kg, SC, or 10 mg/kg, PO) may be appropriate for antimicrobial treatment of alpacas. (Am J Vet Res2005;66:767–771)}, number={5}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Gandolf, A. Rae and Papich, Mark G. and Bringardner, Amy B. and Atkinson, Mark W.}, year={2005}, month={May}, pages={767–771} }
 @article{rush_hunter_papich_raphael_calle_clippinger_cook_2005, title={Pharmacokinetics and Safety of Acyclovir in Tragopans (Tragopan species)}, volume={19}, ISSN={1082-6742}, url={http://dx.doi.org/10.1647/2004-026.1}, DOI={10.1647/2004-026.1}, abstractNote={Abstract In response to multiple peracute deaths caused by herpesvirus in several pheasant species, a study was designed to determine the absorption, distribution, and linearity of acyclovir in hybrid tragopans (Tragopan caboti × Tragopan temminckii). Acyclovir was administered to 5 healthy adult tragopans, 3 males and 2 females, in a single dose of 40, 80, or 120 mg/kg PO. Blood samples were collected at 1, 2, 6, 12, and 24 hours after administration, and concentrations of acyclovir were measured by reverse phase high-performance liquid chromatography (HPLC) with a C-8 column and ultraviolet (UV) detection. Although plasma concentrations were not linear, results from this study suggest that a dosage of 120 mg/kg PO q12h in tragopans may achieve effective plasma concentrations (1.0 μg/ml) for potential treatment and prevention of herpesviral infections. However, further studies are needed to determine if this dosage is safe for repeated administration.}, number={4}, journal={Journal of Avian Medicine and Surgery}, publisher={Association of Avian Veterinarians (AAV)}, author={Rush, Elizabeth Marie and Hunter, Robert P. and Papich, Mark and Raphael, Bonnie L. and Calle, Paul P. and Clippinger, Tracy L. and Cook, Robert A.}, year={2005}, month={Dec}, pages={271–276} }
 @article{davis_salmon_papich_2005, title={Pharmacokinetics and tissue distribution of itraconazole after oral and intravenous administration to horses}, volume={66}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2005.66.1694}, abstractNote={AbstractObjective—To determine the pharmacokinetics of itraconazole after IV or oral administration of a solution or capsules to horses and to examine disposition of itraconazole in the interstitial fluid (ISF), aqueous humor, and polymorphonuclear leukocytes after oral administration of the solution.Animals—6 healthy horses.Procedure—Horses were administered itraconazole solution (5 mg/kg) by nasogastric tube, and samples of plasma, ISF, aqueous humor, and leukocytes were obtained. Horses were then administered itraconazole capsules (5 mg/kg), and plasma was obtained. Three horses were administered itraconazole (1.5 mg/kg, IV), and plasma samples were obtained. All samples were analyzed by use of high-performance liquid chromatography. Plasma protein binding was determined. Data were analyzed by compartmental and noncompartmental pharmacokinetic methods.Results—Itraconazole reached higher mean ± SD plasma concentrations after administration of the solution (0.41 ± 0.13 µg/mL) versus the capsules (0.15 ± 0.12 µg/mL). Bioavailability after administration of capsules relative to solution was 33.83 ± 33.08%. Similar to other species, itraconazole has a high volume of distribution (6.3 ± 0.94 L/kg) and a long half-life (11.3 ± 2.84 hours). Itraconazole was not detected in the ISF, aqueous humor, or leukocytes. Plasma protein binding was 98.81 ± 0.17%.Conclusions and Clinical Relevance—Itraconazole administered orally as a solution had higher, more consistent absorption than orally administered capsules and attained plasma concentrations that are inhibitory against fungi that infect horses. Administration of itraconazole solution (5 mg/kg, PO, q 24 h) is suggested for use in clinical trials to test the efficacy of itraconazole in horses. (Am J Vet Res2005;66:1694–1701)}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Davis, JL and Salmon, JH and Papich, MG}, year={2005}, month={Oct}, pages={1694–1701} }
 @article{davis_salmon_papich_2005, title={Pharmacokinetics and tissue fluid distribution of cephalexin in the horse after oral and i.v. administration}, volume={28}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2005.00683.x}, abstractNote={The purpose of this study was to determine the pharmacokinetics and tissue fluid distribution of cephalexin in the adult horse following oral and i.v. administration. Cephalexin hydrate (10 mg/kg) was administered to horses i.v. and plasma samples were collected. Following a washout period, cephalexin (30 mg/kg) was administered intragastrically. Plasma, interstitial fluid (ISF) aqueous humor, and urine samples were collected. All samples were analyzed by high‐pressure liquid chromatography (HPLC). Following i.v. administration, cephalexin had a plasma half‐life (t1/2) of 2.02 h and volume of distribution [Vd(ss)] of 0.25 L/kg. Following oral administration, the average maximum plasma concentration (Cmax) was 3.47 μg/mL and an apparent half‐life (t1/2) of 1.64 h. Bioavailability was approximately 5.0%. The AUCISF:AUCplasma ratio was 80.55% which corresponded to the percentage protein‐unbound drug in the plasma (77.07%). The t1/2 in the ISF was 2.49 h. Cephalexin was not detected in the aqueous humor. The octanol:water partition coefficient was 0.076 ± 0.025. Cephalexin was concentrated in the urine with an average concentration of 47.59 μg/mL. No adverse events were noted during this study. This study showed that cephalexin at a dose of 30 mg/kg administered orally at 8 h dosage intervals in horses can produce plasma and interstitial fluid drug concentrations that are in a range recommended to treat susceptible gram‐positive bacteria (MIC ≤ 0.5 μg/mL). Because of the low oral bioavailability of cephalexin in the horse, the effect of chronic dosing on the normal intestinal bacterial flora requires further investigation.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Davis, JL and Salmon, JH and Papich, MG}, year={2005}, month={Oct}, pages={425–431} }
 @article{sanchez_murray_isaza_papich_2005, title={Pharmacokinetics of a single dose of enrofloxacin administered orally to captive Asian elephants (Elephas maximus)}, volume={66}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2005.66.1948}, abstractNote={AbstractObjective—To determine the pharmacokinetics of enrofloxacin after oral administration to captive elephants.Animals—6 clinically normal adult Asian elephants (Elephas maximus).Procedure—Each elephant received a single dose of enrofloxacin (2.5 mg/kg, PO). Three elephants received their complete diet (pellets and grain) within 2 hours after enrofloxacin administration, whereas the other 3 elephants received only hay within 6 hours after enrofloxacin administration. Serum concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography.Results—Harmonic mean half-life after oral administration was 18.4 hours for all elephants. Mean ± SD peak serum concentration of enrofloxacin was 1.31 ± 0.40 µg/mL at 5.0 ± 4.2 hours after administration. Mean area under the curve was 20.72 ± 4.25 (µg × h)/mL.Conclusions and Clinical Relevance—Oral administration of enrofloxacin to Asian elephants has a prolonged elimination half-life, compared with the elimination half-life for adult horses. In addition, potentially therapeutic concentrations in elephants were obtained when enrofloxacin was administered orally at a dosage of 2.5 mg/kg. Analysis of these results suggests that enrofloxacin administered with feed in the manner described in this study could be a potentially useful antimicrobial for use in treatment of captive Asian elephants with infections attributable to organisms, such asBordetellaspp,Escherichia coli,Mycoplasmaspp,Pasteurellaspp,Haemophilusspp,Salmonellaspp, andStaphylococcusspp. (Am J Vet Res2005;66:1948–1953)}, number={11}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Sanchez, CR and Murray, SZ and Isaza, R and Papich, MG}, year={2005}, month={Nov}, pages={1948–1953} }
 @article{wilkins_papich_sweeney_2005, title={Pharmacokinetics of acyclovir in adult horses}, volume={15}, ISSN={1479-3261 1476-4431}, url={http://dx.doi.org/10.1111/j.1476-4431.2005.00145.x}, DOI={10.1111/j.1476-4431.2005.00145.x}, abstractNote={AbstractObjective:To determine the pharmacokinetics of acyclovir administered intravenously (IV) and orally to healthy adult horses.Design:Random cross‐over with an approximate 1‐week washout period between trials.Setting:University veterinary medical teaching hospital.Animals:Six healthy adult research herd horses.Interventions and main results:Acyclovir was administered IV (10 mg/kg in 1 L isotonic crystalloid solution over 60 minutes) and orally (20 mg/kg) to healthy adult horses. Plasma samples were obtained and acyclovir concentrations were determined by high‐pressure liquid chromatography. Peak concentration (mean±SD) for IV acyclovir was 13.74±5.88 μg/mL at the completion of the 1‐hour infusion. The half‐life of the distribution phase (α) was 0.16 hours while the half‐life of the elimination phase (β) was 9.6 hours. The steady‐state volume of distribution was 3.93±1.21 L/kg. We were unable to measure pharmacokinetics after PO acyclovir as plasma concentrations were below the lower limits of detection in all 6 horses.Conclusions:IV administration of acyclovir to healthy adult horses achieves concentrations within the sensitivity range described for equine herpes virus‐type 1. The oral bioavailability of acyclovir in horses is low and additional studies are required.}, number={3}, journal={Journal of Veterinary Emergency and Critical Care}, publisher={Wiley}, author={Wilkins, Pamela A. and Papich, Mark and Sweeney, Raymond W.}, year={2005}, month={Sep}, pages={174–178} }
 @article{lewbart_papich_whitt-smith_2005, title={Pharmacokinetics of florfenicol in the red pacu (Piaractus brachypomus) after single dose intramuscular administration}, volume={28}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2005.00641.x}, abstractNote={Florfenicol is a structural analogue of chloramphenicol similar to thiamphenicol, but with more activity against some bacteria than chloramphenicol (Cannon et al., 1990). Florfenicol works by inhibiting bacterial protein synthesis at the ribosome (Cannon et al., 1990). Florfenicol activity against bacteria differs from chloramphenicol because florfenicol is not susceptible to the same resistance mechanisms as chloramphenicol (Papich & Riviere, 2001). Organisms resistant to chloramphenicol may still be susceptible to florfenicol. Florfenicol has been demonstrated to be efficacious against bacteria (e.g. Aeromonas salmonicida, Vibrio salmonicida, and Edwardsiella ictaluri) of fish, especially salmonids and catfish (Fukui et al., 1987; Inglis & Richards, 1991; Inglis et al., 1991; Nordmo et al., 1994,1998; Samuelsen et al., 1998; Gaunt et al., 2003,2004). Florfenicol has been proven to be clinically effective in controlling a variety of bacterial diseases in salmonids and is approved for use in Europe, Norway, Canada, Japan, and South Korea for a variety of fish species (Gaunt et al., 2003). Florfenicol has been administered orally for treatment of bacterial infections of captive fish in Europe and Canada under the trade names Aquafen and Aquaflor (Schering-Plough, Kenilworth, NJ, USA), respectively. In rainbow trout (Oncorhyncus mykiss) kept at 10 C, an oral dose of 10 mg/kg had a mean residence time of 21 h and a Cmax of 3.23 mcg/mL (Pinault et al., 1997). Pharmacokinetics have also been described for Atlantic salmon, Salmo salar (Martinsen et al., 1993). Other work has determined florfenicol to be safe and effective for the treatment of E. ictaluri (enteric septicemia of catfish) in channel catfish (Ictalurus punctatus) when administered orally in feed (Gaunt et al., 2003, 2004). The objectives of this study were to determine the maximum serum concentrations, elimination half-life, and relative bioavailability of florfenicol in the red pacu following single-dose intramuscular (i.m.) administration. We used 16 red pacu for the study. Fish were of uniform age and size (approximately 3.5 years old and weighing 400–500 g each). Fish were individually maintained in sixteen 75 L aquariums which all shared a common water supply via a recirculating system. Important water quality parameters such as temperature (25 C), pH 7.2, total alkalinity (51.0 mg/L), and specific gravity (1.000) were frequently monitored and actively maintained. Twelve fish were weighed immediately prior to epaxial i.m. dosing with 10.0 mg/kg florfenicol (NuFlor , Schering-Plough). The four control fish received equivalent volumes of i.m. saline. Fish were manually restrained and approximately 0.4 mL of blood was taken from the caudal vein from each fish and four control fish using a sodium heparinized 1 cc syringe with a 25 G needle at the following times postdrug administration: 0, 3, 4, 6, 9, 12, 24, 48, and 72 h. The four control fish were used to determine if any residual or excreted florfenicol in the recirculating system was absorbed by the study pacu. Florfenicol plasma concentrations were analyzed with reversephase high performance liquid chromatography (HPLC). The HPLC apparatus consisted of a pump (Waters Model 600 Pump; Millipore Corp., Milford, MA, USA), autosampler (Hewlett Packard Series 1050 Autosampler; Hewlett Packard, Palo Alto, CA, USA), UV detector (HP Series 1050 UV detector; Hewlett Packard), and computer for data collection and analysis (Hewlett Packard HPLC ChemStation running Windows 3.1 on a Hewlett Packard Vectra 486/33N computer). Eluates were separated with a C-8 reverse-phase HPLC column (Zorbax RXC8 4.6 mm · 15 cm; 5 lm MAC-MOD Analytical Inc., Chadds Ford, PA, USA). A guard column containing identical packing material also was used (Zorbax RX-C18, 4 mm · 1.25 cm guard column). Florfenicol was eluted with a mobile phase consisting of 73% distilled water and 27% (v/v) acetonitrile. No buffers or mobile phase modifiers were added. The mobile phase was filtered and degassed prior to use and was continuously sparged with helium during the analysis. The flow rate was 1.0 mL/min. Injection volume was 20 mcL. Florfenicol was detected with UV detection at a wavelength of 223 nm. Retention time for florfenicol was approximately 5.5–6.5 min. J. vet. Pharmacol. Therap. 28, 317–319, 2005. SHORT COMMUNICATION}, number={3}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Lewbart, GA and Papich, MG and Whitt-Smith, D}, year={2005}, month={Jun}, pages={317–319} }
 @article{kukanich_lascelles_papich_2005, title={Pharmacokinetics of morphine and plasma concentrations of morphine-6-glucuronide following morphine administration to dogs}, volume={28}, ISSN={["1365-2885"]}, url={https://dx.doi.org/10.1111/j.1365-2885.2005.00661.x}, DOI={10.1111/j.1365-2885.2005.00661.x}, abstractNote={The purpose of this study was to evaluate the pharmacokinetics of morphine and morphine‐6‐glucuronide (M‐6‐G) following morphine administered intravenously and orally to dogs in a randomized crossover design. Six healthy 3–4‐year‐old Beagle dogs were administered morphine sulfate (0.5 mg/kg) as an i.v. bolus and extended release tablets were administered orally as whole tablets (1.6 ± 0.1 mg/kg) in a randomized crossover design. Plasma concentrations of morphine and M‐6‐G were determined using high‐pressure liquid chromatography and electrochemical coulometric detection. Following i.v. administration all dogs exhibited dysphoria and sedation, and four or six dogs vomited. Mean ± SE values for half‐life, apparent volume of distribution, and clearance after i.v. administration were 1.16 ± 0.15 h, 4.55 ± 0.17 L/kg, and 62.46 ± 10.44 mL/min/kg, respectively. One dog vomited following oral administration and was excluded from the oral analysis. Oral bioavailability was 5% as determined from naïve‐averaged analysis. The M‐6‐G was not detected in any plasma samples following oral or i.v. administration of morphine at a 25 ng/mL the limit of quantification. Computer simulations concluded morphine sulfate administered 0.5 mg/kg intravenously every 2 h would maintain morphine plasma concentrations consistent with analgesic plasma concentrations in humans. Oral morphine is poorly and erratically absorbed in dogs.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Kukanich, B and Lascelles, BDX and Papich, MG}, year={2005}, month={Aug}, pages={371–376} }
 @article{poulsen_smith_davis_papich_2005, title={Pharmacokinetics of oral omeprazole in llamas}, volume={28}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2005.00696.x}, abstractNote={Gastrogard®, an oral formulation of omeprazole, was given to six llamas at a dose of 4 mg/kg once a day for 6 days. Plasma samples were collected at 0, 15, 30, 45, and 60 min and 2, 3, 4, 6, 8, 12, and 24 h on days 1 and 6. Plasma omeprazole concentrations were measured by high‐pressure liquid chromatography with ultraviolet detection. Pharmacokinetic parameters calculated included the area under the curve (AUC0‐‐∞), peak plasma concentration (Cmax), time of peak plasma concentration (Tmax), and terminal half‐life (t1/2). On day 6, plasma omeprazole concentrations reached aCmaxof 0.12 μg/mL at aTmaxof 45 min. Thet1/2of omeprazole was 2.3 h and theAUC0‐‐∞was 0.38 h·μg/mL. Plasma concentrations remained above the minimum concentration for inhibition of gastric acid secretion projected from other studies on day 6 in all the llamas for approximately 6 h. However, theAUC0‐‐∞was below the concentrations associated with clinical efficacy. It was not possible to measure oral systemic bioavailability because there was no i.v. data collected from these animals. However, using data published on the i.v. pharmacokinetics of omeprazole in llamas, oral absorption was estimated to be only 2.95%. Due to low absorption the oral dose was increased to 8 and 12 mg/kg and studies were repeated. There were no significant differences inCmax,Tmax, orAUC0‐‐∞for either of the increased doses. These results indicate that after 6 days of treatment with doses up to 12 mg/kg, oral omeprazole produced plasma drug concentrations which are not likely to be associated with clinical efficacy in camelids.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Poulsen, KP and Smith, GW and Davis, JL and Papich, MG}, year={2005}, month={Dec}, pages={539–543} }
 @article{bidgood_papich_2005, title={Plasma and interstitial fluid pharmacokinetics of enrofloxacin, its metabolite ciprofloxacin, and marbofloxacin after oral administration and a constant rate intravenous infusion in dogs}, volume={28}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2005.00664.x}, abstractNote={Enrofloxacin and marbofloxacin were administered to six healthy dogs in separate crossover experiments as a single oral dose (5 mg/kg) and as a constant rate IV infusion (1.24 and 0.12 mg/h·kg, respectively) following a loading dose (4.47 and 2 mg/kg, respectively) to achieve a steady‐state concentration of approximately 1 μg/mL for 8 h. Interstitial fluid (ISF) was collected with anin vivoultrafiltration device at the same time period as plasma to measure protein unbound drug concentrations at the tissue site and assess the dynamics of drug distribution. Plasma and ISF were analyzed for enrofloxacin, its active metabolite ciprofloxacin, and for marbofloxacin by high performance liquid chromatography (HPLC). Lipophilicity and protein binding of enrofloxacin were higher than for marbofloxacin and ciprofloxacin. Compared to enrofloxacin, marbofloxacin had a longer half‐life, higherCmax, and largerAUC0−∞in plasma and ISF after oral administration. Establishing steady state allowed an assessment of the dynamics of drug concentrations between plasma and ISF. The ISF and plasma‐unbound concentrations were similar during the steady‐state period despite differences in lipophilicity and pharmacokinetic parameters of the drugs.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Bidgood, TL and Papich, MG}, year={2005}, month={Aug}, pages={329–341} }
 @book{maddison_papich_2005, title={Small Animal Medicine: The Year in Small Animal Medicine}, volume={1}, publisher={Blackwell Publishing}, year={2005} }
 @article{kukanich_lascelles_aman_mealey_papich_2005, title={The effects of inhibiting cytochrome P450 3A, p-glycoprotein, and gastric acid secretion on the oral bioavailability of methadone in dogs}, volume={28}, ISSN={["1365-2885"]}, url={https://dx.doi.org/10.1111/j.1365-2885.2005.00681.x}, DOI={10.1111/j.1365-2885.2005.00681.x}, abstractNote={Methadone is an opioid, which has a high oral bioavailability (>70%) and a long elimination half‐life (>20 h) in human beings. The purpose of this study was to evaluate the effects of ketoconazole [a CYP3A and p‐glycoprotein (p‐gp) inhibitor] and omeprazole (an H+,K+‐ATPase proton‐pump inhibitor) on oral methadone bioavailability in dogs. Six healthy dogs were used in a crossover design. Methadone was administered i.v. (1 mg/kg), orally (2 mg/kg), again orally following oral ketoconazole (10 mg/kg q12 h for two doses), and following omeprazole (1 mg/kg p.o. q12 h for five doses). Plasma concentrations of methadone were analyzed by high‐pressure liquid chromatography or fluorescence polarization immunoassay. The mean ± SD for the elimination half‐life, volume of distribution, and clearance were 1.75 ± 0.25 h, 3.46 ± 1.09 L/kg, and 25.14 ± 9.79 mL/min·kg, respectively following i.v. administration. Methadone was not detected in any sample following oral administration alone or following oral administration with omeprazole. Following administration with ketoconazole, detectable concentrations of methadone were present in one dog with a 29% bioavailability. MDR‐1 genotyping, encoding p‐gp, was normal in all dogs. In contrast to its pharmacokinetics humans, methadone has a short elimination half‐life, rapid clearance, and low oral bioavailability in dogs and the extent of absorption is not affected by inhibition of CYP3A, p‐gp, and gastric acid secretion.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, publisher={Blackwell Science Ltd Oxford, UK}, author={KuKanich, B and Lascelles, BDX and Aman, AM and Mealey, KL and Papich, MG}, year={2005}, month={Oct}, pages={461–466} }
 @article{kukanich_lascelles_papich_2005, title={Use of a von Frey device for evaluation of pharmacokinetics and pharmacodynamics of morphine after intravenous administration as an infusion or multiple doses in dogs}, volume={66}, ISSN={["0002-9645"]}, url={https://dx.doi.org/10.2460/ajvr.2005.66.1968}, DOI={10.2460/ajvr.2005.66.1968}, abstractNote={AbstractObjective—To evaluate the pharmacokinetics and pharmacodynamics of morphine after IV administration as an infusion or multiple doses in dogs by use of a von Frey (vF) device.Animals—6 dogs.Procedure—In the first 2 crossover experiments of a 3-way crossover study, morphine or saline (0.9%) solution was administered via IV infusion. Loading doses and infusion rates were administered to attain targeted plasma concentrations of 10, 20, 30, and 40 ng/mL. In the third experiment, morphine (0.5 mg/kg) was administered IV every 2 hours for 3 doses. The vF thresholds were measured hourly for 8 hours. Plasma concentrations of morphine were measured by highpressure liquid chromatography.Results—No significant changes in vF thresholds were observed during infusion of saline solution. The vF thresholds were significantly increased from 5 to 8 hours during the infusion phase, corresponding to targeted morphine plasma concentrations > 30 ng/mL and infusion rates ≥ 0.15 ± 0.02 mg/kg/h. The maximal effect (EMAX) was 78 ± 11% (percentage change from baseline), and the effective concentration to attain a 50% maximal response (EC50) was 29.5 ± 5.4 ng/mL. The vF thresholds were significantly increased from 1 to 7 hours during the multiple-dose phase; the EC50and EMAX were 23.9 ± 4.7 ng/mL and 173 ± 58%, respectively. No significant differences in half-life, volume of distribution, or clearance between the first and last dose of morphine were detected.Conclusions and Clinical Relevance—Morphine administered via IV infusion (0.15 ± 0.02 mg/kg/h) and multiple doses (0.5 mg/kg, IV, every 2 hours for 3 doses) maintained significant antinociception in dogs. (Am J Vet Res2005;66:1968–1974)}, number={11}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={KuKanich, B and Lascelles, BDX and Papich, MG}, year={2005}, month={Nov}, pages={1968–1974} }
 @article{kukanich_lascelles_papich_2005, title={Validation of a high-pressure liquid chromatography and fluorescence polarization immunoassay for the determination of methadone in canine plasma}, volume={27}, ISSN={["0163-4356"]}, url={https://dx.doi.org/10.1097/01.ftd.0000158078.15459.90}, DOI={10.1097/01.ftd.0000158078.15459.90}, abstractNote={Methadone is a synthetic opiate derivative that possesses analgesic activity. A modified fluorescence polarization immunoassay (FPIA) method and a high-pressure liquid chromatography (HPLC) method with UV detection were compared for measurement of concentrations of methadone in canine plasma following intravenous and oral methadone administration. The mean ± SD for accuracy (deviation from actual concentration) and precision (coefficient of variation) when methadone-fortified canine plasma was evaluated with the FPIA method were 3.9 ± 3.2% and 4.4 ± 2.9%, respectively. The accuracy and precision of the HPLC method were 6.2 ± 5.2% and 7.7 ± 3.9%, respectively. The limit of quantification for the FPIA and HPLC methods were 25 and 20 ng/mL, respectively. The coefficient of determination (r2) between FPIA and HPLC analysis was 0.94 when plasma from dogs dosed with methadone was evaluated. FPIA provides a rapid, sensitive, and specific measurement of methadone in canine plasma following oral and intravenous administration.}, number={3}, journal={THERAPEUTIC DRUG MONITORING}, publisher={LWW}, author={KuKanich, B and Lascelles, BDX and Papich, MG}, year={2005}, month={Jun}, pages={389–392} }
 @inbook{martinez_hungerford_papich_2005, title={Veterinary Pharmaceuticals: Factors Influencing their Development and Use}, booktitle={Encyclopedia of Pharmaceutical Technology}, publisher={Taylor & Francis}, author={Martinez, M.N. and Hungerford, L. and Papich, M.G.}, year={2005} }
 @article{cox_cottrell_smith_papich_frazier_bartges_2004, title={Allometric analysis of ciprofloxacin and enrofloxacin pharmacokinetics across species}, volume={27}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2004.00560.x}, abstractNote={The purpose of this study was to examine the allometric analysis of ciprofloxacin and enrofloxacin using pharmacokinetic data from the literature. The pharmacokinetic parameters used were half‐life, clearance and volume of distribution. Relationships between body weight and the pharmacokinetic parameter were based on the empirical formula Y = aWb, where Y is half‐life, clearance or volume of distribution, W the body weight and a is an allometric coefficient (intercept) that is constant for a given drug. The exponential term b is a proportionality constant that describes the relationship between the pharmacokinetic parameter of interest and body weight. A total of 21 different species of animals were studied. Results of the allometric analyses indicated similarity between clearance and volume of distribution as they related to body weight for both drugs. Results of the current analyses indicate it is possible to use allometry to predict pharmacokinetic variables of enrofloxacin or ciprofloxacin based on body size of species. This could provide information on appropriate doses of ciprofloxacin and enrofloxacin for all species.}, number={3}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Cox, SK and Cottrell, MB and Smith, L and Papich, MG and Frazier, DL and Bartges, J}, year={2004}, month={Jun}, pages={139–146} }
 @book{brown_papich_prescott_sousa_meikle_gorman_2004, place={Parsippany-Troy Hills, NJ}, title={Cephalosporins in veterinary medicine}, publisher={Pfizer Animal Health}, author={Brown, S.A. and Papich, Mark G. and Prescott, John F. and Sousa, Candace A. and Meikle, Stuart and Gorman, Mary Pat}, year={2004} }
 @article{gardner_atkins_sams_schwabenton_papich_2004, title={Characterization of the Pharmacokinetic and Pharmacodynamic Properties of the Angiotensin-Converting Enzyme Inhibitor, Enalapril, in Horses}, volume={18}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2004.tb00166.x}, DOI={10.1111/j.1939-1676.2004.tb00166.x}, abstractNote={The pharmacokinetics of enalapril (0.5 mg/kg IV) and the pharmacodynamics of enalapril (0.5 mg/kg PO) in 5 mares were investigated. After single IV dosing, concentrations of enalapril and enalaprilat, its active metabolite, were measured. Two weeks later, enalapril was administered by nasogastric tube. Potassium, creatinine, blood urea nitrogen (BUN), enalapril, and enalaprilat concentrations and angiotensin converting enzyme (ACE) activity were measured in serum. In addition, heart rate, blood pressure, digital venous blood gases, and lactate were measured. Two weeks later, enalapril was again administered by nasogastric tube. To mimic activation of the renin‐angiotensin‐aldosterone system, angiotensin I (0.5 μg/kg) was administered at fixed intervals, followed by blood‐pressure and heart‐rate measurement. The elimination half lives of enalapril and enalaprilat were 0.59 and 1.25 hours, respectively, after IV administration. After PO administration, enalapril and enalaprilat were not detectable in serum. There was a tendency(P= .0625) toward a decrease in ACE activity 45–120 minutes after enalapril administration, but ACE activity suppression was never >16%. There was a tendency(P= .0625) toward a decrease in mean arterial pressure (MAP) 6–8 hours after enalapril administration. Serum concentrations of potassium, creatinine, and BUN and digital venous blood gases and lactate concentrations did not change. In response to angiotensin I, there was a tendency(P= .0625) toward a decrease in the MAP response 4–24 hours after enalapril administration. Single‐dose enalapril at 0.5 mg/kg PO did not demonstrate significant availability, pharmacodynamic effect, or substantial suppression of ACE activity.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Gardner, Sarah Y. and Atkins, Clarke E. and Sams, Richard A. and Schwabenton, A. Brooke and Papich, Mark G.}, year={2004}, month={Mar}, pages={231–237} }
 @article{kukanich_papich_huff_stoskopf_2004, title={Comparison of amikacin pharmacokinetics in a killer whale (Orcinus orca) and a beluga whale (Delphinapterus leucas)}, volume={35}, ISSN={["1042-7260"]}, DOI={10.1638/03-078}, abstractNote={Abstract Amikacin, an aminoglycoside antimicrobial, was administered to a killer whale (Orcinus orca) and a beluga whale (Delphinapterus leucas) for the treatment of clinical signs consistent with gram-negative aerobic bacterial infections. Dosage regimens were designed to target a maximal plasma concentration 8–10 times the minimum inhibitory concentrations of the pathogen and to reduce the risk of aminoglycoside toxicity. Allometric analysis of published pharmacokinetic parameters in mature animals yielded a relationship for amikacin's volume of distribution, in milliliters, given by the equation Vd = 151.058(BW)1.043. An initial dose for amikacin was estimated by calculating the volume of distribution and targeted maximal concentration. With this information, dosage regimens for i.m. administration were designed for a killer whale and a beluga whale. Therapeutic drug monitoring was performed on each whale to assess the individual pharmacokinetic parameters. The elimination half-life (5.99 hr), volume of distribution per bioavailability (319 ml/kg), and clearance per bioavailability (0.61 ml/min/kg) were calculated for the killer whale. The elimination half-life (5.03 hr), volume of distribution per bioavailability (229 ml/kg), and clearance per bioavailability (0.53 ml/ min/kg) were calculated for the beluga whale. The volume of distribution predicted from the allometric equation for both whales was similar to the calculated pharmacokinetic parameter. Both whales exhibited a prolonged elimination half-life and decreased clearance when compared with other animal species despite normal renal parameters on biochemistry panels. Allometric principles and therapeutic drug monitoring were used to accurately determine the doses in these cases and to avoid toxicity.}, number={2}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={KuKanich, B and Papich, M and Huff, D and Stoskopf, M}, year={2004}, month={Jun}, pages={179–184} }
 @inbook{papich_2004, place={Quedgeley, Gloucester, England}, title={Drug therapy for diseases of the central nervous system}, booktitle={BSAVA Manual of Canine and Feline Neurology}, publisher={British Small Animal Veterinary Association}, author={Papich, M.G.}, editor={Platt, S.R. and Olby, N.J.Editors}, year={2004}, pages={368–384} }
 @article{sellon_roberts_blikslager_ulibarri_papich_2004, title={Effects of continuous rate intravenous infusion of butorphanol on physiologic and outcome variables in horses after celiotomy}, volume={18}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2004)18<555:EOCRII>2.0.CO;2}, abstractNote={A randomized, controlled, blinded clinical trial was performed to determine whether butorphanol administered by continuous rate infusion (CRI) for 24 hours after abdominal surgery would decrease pain and surgical stress responses and improve recovery in horses. Thirty-one horses undergoing exploratory celiotomy for abdominal pain were randomly assigned to receive butorphanol CRI (13 microg/kg/h for 24 hours after surgery; treatment) or isotonic saline (control). All horses received flunixin meglumine (1.1 mg/kg IV q12h). There were no significant differences between treatment and control horses in preoperative or operative variables. Treatment horses had significantly lower plasma cortisol concentration compared with control horses at 2, 8, 12, 24, 36, and 48 hours after surgery. Mean weight loss while hospitalized was significantly less for treatment horses than control horses, whether expressed as total decrease in body weight (13.9+/-3.4 and 27.9+/-4.5 kg, respectively) or as a percentage decrease in body weight (2.6+/-0.7 and 6.3+/-1.1%, respectively). Treatment horses were significantly delayed in time to first passage of feces (median times of 15 and 4 hours, respectively). Treatment horses had significantly improved behavior scores during the first 24 hours after surgery, consistent with the conclusion that they experienced less pain during that time. Butorphanol CRI during the immediate postoperative period significantly decreased plasma cortisol concentrations and improved recovery characteristics in horses undergoing abdominal surgery.}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Sellon, DC and Roberts, MC and Blikslager, AT and Ulibarri, C and Papich, MG}, year={2004}, pages={555–563} }
 @article{bowman_waldoch_pittman_papich_hartup_2004, title={Enrofloxacin and ciprofloxacin plasma concentrations in sandhill cranes (Grus canadensis) after enrofloxacin administration in drinking water}, volume={18}, ISSN={["1938-2871"]}, DOI={10.1647/2003-020}, abstractNote={Abstract Bacterial diseases are common in captive cranes. Administration of antimicrobial drugs in the drinking water could provide a nonstressful means of treatment in these birds. This preliminary study was conducted to determine if therapeutic plasma concentrations of enrofloxacin, its primary active metabolite ciprofloxacin, or both, could be achieved and maintained in sandhill cranes (Grus canadensis) after administration in drinking water at a concentration of 50 ppm. Drinking water medicated with enrofloxacin was provided ad libitum to 8 healthy sandhill cranes (4 housed individually and 4 housed in pairs) for 14 days. Mean enrofloxacin plasma concentrations (±SD) were 0.03 (±0.02), 0.03 (±0.02), 0.02 (±0.01), and 0.01 (±0.00) μg/ml on days 2, 6, 10, and 14, respectively. Mean ciprofloxacin plasma concentrations paralleled those of enrofloxacin but were slightly lower, ranging from 0.01 to 0.02 μg/ml. Enrofloxacin and ciprofloxacin concentrations both were below accepted therapeutic plasma concentrations for birds. Based on the plasma concentrations achieved in this preliminary study and the minimum inhibitory concentration values for bacteria commonly isolated from poultry species, enrofloxacin-medicated water would only be effective for treating infections of highly susceptible bacteria in sandhill cranes.}, number={3}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Bowman, MR and Waldoch, JA and Pittman, JM and Papich, MG and Hartup, BK}, year={2004}, month={Sep}, pages={144–150} }
 @article{bach_kukanich_papich_mckiernan_2004, title={Evaluation of the bioavailability and pharmacokinetics of two extended-release theophylline formulations in dogs}, volume={224}, ISSN={["1943-569X"]}, DOI={10.2460/javma.2004.224.1113}, abstractNote={Abstract
				
					Objective—To evaluate the bioavailability and pharmacokinetic
characteristics of 2 commercially available
extended-release theophylline formulations in
dogs.
				
					Design—Randomized 3-way crossover study.
				
					Animals—6 healthy adult dogs.
				
					Procedure—A single dose of aminophylline (11 mg·kg–1
[5 mg·lb–1], IV, equivalent to 8.6 mg of theophylline/kg
[3.9 mg·lb–1]) or extended-release theophylline tablets
(mean dose, 15.5 mg·kg–1 [7.04 mg·lb–1], PO) or capsules
(mean dose, 15.45 mg·kg–1 [7.02 mg·lb–1], PO) was
administered to all dogs. Blood samples were obtained
at various times for 36 hours after dosing; plasma was
separated and immediately frozen. Plasma samples
were analyzed by use of fluorescence polarization
immunoassay.
				
					Results—Administration of theophylline IV best fit a
2-compartment model with rapid distribution followed
by slow elimination. Administration of extended-release
theophylline tablets and capsules best fit a 1-
compartment model with an absorption phase. Mean
values for plasma terminal half-life, volume of distribution,
and systemic clearance were 8.4 hours, 0.546
L·kg–1, and 0.780 mL·kg–1·min–1, respectively, after IV
administration of theophylline. Systemic availability
was > 80% for both oral formulations. Computer simulations
predicted that extended-release theophylline
tablets or capsules administered at a dosage of 10
mg·kg–1 (4.5 mg·lb–1), PO, every 12 hours would maintain
plasma concentrations within the desired therapeutic
range of 10 to 20 µg·mL–1.
				
					Conclusions and Clinical Relevance—Results of
these single-dose studies indicated that administration
of the specific brand of extended-release theophylline
tablets or capsules used in this study at a
dosage of 10 mg·kg–1, PO, every 12 hours would
maintain plasma concentrations within the desired
therapeutic range (10 to 20 µg·mL–1) in healthy dogs.
(J Am Vet Med Assoc 2004;224:1113–1119)}, number={7}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Bach, JF and Kukanich, B and Papich, MG and McKiernan, BC}, year={2004}, month={Apr}, pages={1113–1119} }
 @article{gardner_davis_jones_lafevers_hoskins_mcarver_papich_2004, title={Moxifloxacin pharmacokinetics in horses and disposition into phagocytes after oral dosing}, volume={27}, ISSN={["1365-2885"]}, url={http://europepmc.org/abstract/med/14995968}, DOI={10.1046/j.0140-7783.2003.00529.x}, abstractNote={Journal of Veterinary Pharmacology and TherapeuticsVolume 27, Issue 1 p. 57-60 Moxifloxacin pharmacokinetics in horses and disposition into phagocytes after oral dosing S. Y. Gardner, S. Y. Gardner Department of Clinical SciencesSearch for more papers by this authorJ. L. Davis, J. L. Davis Department of Clinical SciencesSearch for more papers by this authorS. L. Jones, S. L. Jones Department of Clinical SciencesSearch for more papers by this authorD. H. LaFevers, D. H. LaFevers Department of Clinical SciencesSearch for more papers by this authorM. S. Hoskins, M. S. Hoskins Department of Clinical SciencesSearch for more papers by this authorE. M. Mcarver, E. M. Mcarver Department of Clinical SciencesSearch for more papers by this authorM. G. Papich, M. G. Papich Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this author S. Y. Gardner, S. Y. Gardner Department of Clinical SciencesSearch for more papers by this authorJ. L. Davis, J. L. Davis Department of Clinical SciencesSearch for more papers by this authorS. L. Jones, S. L. Jones Department of Clinical SciencesSearch for more papers by this authorD. H. LaFevers, D. H. LaFevers Department of Clinical SciencesSearch for more papers by this authorM. S. Hoskins, M. S. Hoskins Department of Clinical SciencesSearch for more papers by this authorE. M. Mcarver, E. M. Mcarver Department of Clinical SciencesSearch for more papers by this authorM. G. Papich, M. G. Papich Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this author First published: 18 February 2004 https://doi.org/10.1046/j.0140-7783.2003.00529.xCitations: 28 Sarah Y. Gardner, Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA. E-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume27, Issue1February 2004Pages 57-60 RelatedInformation}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Gardner, SY and Davis, JL and Jones, SL and Lafevers, DH and Hoskins, MS and Mcarver, M and Papich, MG}, year={2004}, month={Feb}, pages={57–60} }
 @article{seguin_papich_sigle_gibson_levy_2004, title={Pharmackokinetics of enrofloxacin in neonatal kittens}, volume={65}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2004.65.350}, abstractNote={AbstractObjective—To determine the pharmacokinetics of enrofloxacin in neonatal kittens and compare the pharmacokinetics of enrofloxacin in young and adult cats.Animals—7 adult cats and 111 kittens (2 to 8 weeks old).Procedure—A single dose of 5 mg of enrofloxacin/kg was administered to adults (IV) and kittens (IV, SC, or PO). Plasma concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were determined.Results—The half-life of enrofloxacin administered IV in 2-, 6-, and 8-week-old kittens was significantly shorter and its elimination rate significantly greater than that detected in adults. The apparent volumes of distribution were lower at 2 to 4 weeks and greater at 6 to 8 weeks. This resulted in lower peak plasma concentration (Cmax) at 6 to 8 weeks; however, initial plasma concentration was within the therapeutic range after IV administration at all ages. Compared with IV administration, SC injection of enrofloxacin in 2-weekold kittens resulted in similar Cmax, half-life, clearance, and area under the curve values. Enrofloxacin administered via SC injection was well absorbed in 6- and 8- week-old kittens, but greater clearance and apparent volume of distribution resulted in lower plasma concentrations. Oral administration of enrofloxacin resulted in poor bioavailability.Conclusions and Clinical Relevance—In neonatal kittens, IV and SC administration of enrofloxacin provided an effective route of administration. Oral administration of enrofloxacin in kittens did not result in therapeutic drug concentrations. Doses may need to be increased to achieve therapeutic drug concentrations in 6- to 8-week-old kittens. (Am J Vet Res2004;65:350–356)}, number={3}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Seguin, MA and Papich, MG and Sigle, KJ and Gibson, NM and Levy, JK}, year={2004}, month={Mar}, pages={350–356} }
 @article{helmick_papich_vliet_bennett_jacobson_2004, title={Pharmacokinetic disposition of a long-acting oxytetracycline formulation after single-dose intravenous and intramuscular administrations in the American alligator (Alligator mississippiensis)}, volume={35}, ISSN={["1042-7260"]}, DOI={10.1638/03-001}, abstractNote={Abstract The pharmacokinetics of a long-acting oxytetracycline preparation administered i.v. and i.m. to American alligators (Alligator mississippiensis) at 10 mg/kg was determined. Plasma levels of oxytetracycline were measured using high-performance liquid chromatography, and the resulting concentration versus time curve was analyzed using compartmental modeling and noncompartmental modeling techniques for i.v. and i.m. samples, respectively. A two-compartment model best represented the i.v. data. Intravenous administration of oxytetracycline resulted in an extrapolated mean plasma concentration at time zero of 60.63 ± 28.26 μg/ml, with average plasma drug levels of 2.82 ± 0.71 μg/ml at the end of the 192-hr sampling period. Plasma volume of distribution for i.v. oxytetracycline was 0.20 ± 0.09 L/kg, with a harmonic mean elimination half-life of 15.15 hr and mean total body clearance rate of 0.007 ± 0.002 L/hr/kg. Intramuscular administration of oxytetracycline achieved a mean peak plasma concentration of 6.85 ± 1.96 μg/ml at 1 hr after administration, with average plasma drug levels of 4.96 ± 1.97 μg/ml at the end of the 192-hr sampling period. The harmonic mean terminal elimination half-life for i.m. oxytetracycline was 131.23 hr. Based on the results of this study, long-acting preparations of oxytetracycline administered parenterally to American alligators at 10 mg/kg q 5 days is expected to maintain plasma concentrations above the minimum inhibitory concentration of 4.0 μg/ml for susceptible organisms.}, number={3}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Helmick, KE and Papich, MG and Vliet, KA and Bennett, RA and Jacobson, ER}, year={2004}, month={Sep}, pages={341–346} }
 @article{johansson_gardner_levine_papich_lafevers_goldman_sheets_atkins_2004, title={Pharmacokinetics and pharmacodynamics of furosemide after oral administration to horses}, volume={18}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2004)18<739:PAPOFA>2.0.CO;2}, abstractNote={Furosemide is the most common diuretic drug used in horses. Furosemide is routinely administered as IV or IM bolus doses 3-4 times a day. Administration PO is often suggested as an alternative, even though documentation of absorption and efficacy in horses is lacking. This study was carried out in a randomized, crossover design and compared 8-hour urine volume among control horses that received placebo, horses that received furosemide at 1 mg/kg PO, and horses that received furosemide at 1 mg/kg IV. Blood samples for analysis of plasma furosemide concentrations, PCV, and total solids were obtained at specific time points from treated horses. Furosemide concentrations were determined by reversed-phase high-performance liquid chromatography with fluorescent detection. Systemic availability of furosemide PO was poor, erratic, and variable among horses. Median systemic bioavailability was 5.4% (25th percentile, 75th percentile: 3.5, 9.6). Horses that received furosemide IV produced 7.4 L (7.1, 7.7) of urine over the 8-hour period. The maximum plasma concentration of 0.03 microg/mL after administration PO was not sufficient to increase urine volume compared with control horses (1.2 L [1.0, 1.4] PO versus 1.2 L [1.0, 1.4] control). There was a mild decrease in urine specific gravity within 1-2 hours after administration of furosemide PO, and urine specific gravity was significantly lower in horses treated with furosemide PO compared with control horses at the 2-hour time point. Systemic availability of furosemide PO was poor and variable. Furosemide at 1 mg/kg PO did not induce diuresis in horses.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Johansson, AM and Gardner, SY and Levine, JF and Papich, MG and LaFevers, DH and Goldman, RB and Sheets, MK and Atkins, CE}, year={2004}, pages={739–743} }
 @article{helmick_papich_vliet_bennett_bennett_jacobson_2004, title={Pharmacokinetics of enrofloxacin after single-dose oral and intravenous administration in the American alligator (Alligator mississippiensis)}, volume={35}, ISSN={["1937-2825"]}, DOI={10.1638/03-002}, abstractNote={Abstract The pharmacokinetics of enrofloxacin administered orally and i.v. to American alligators (Alligator mississippiensis) at 5 mg/kg was determined. Plasma levels of enrofloxacin and its metabolite ciprofloxacin were measured using high-performance liquid chromatography and the resulting concentration versus time curve analyzed using compartmental modeling techniques for the i.v. data and noncompartmental modeling techniques for the oral data. A two-compartment model best represented the i.v. data. Intravenous administration of enrofloxacin resulted in an extrapolated mean plasma concentration of 4.19 ± 4.23 μg/ml at time zero, with average plasma drug levels remaining above 1.0 μg/ml for an average of 36 hr. Plasma volume of distribution for i.v. enrofloxacin was 1.88 ± 0.96 L/kg, with a harmonic mean elimination half-life of 21.05 hr and mean total body clearance rate of 0.047 ± 0.021 L/hr/kg. Plasma levels of p.o. enrofloxacin remained below 1.0 μg/ml in all test animals, and average concentrations ranged from 0.08 to 0.50 μg/ml throughout the sampling period. Oral administration of enrofloxacin achieved a mean maximum plasma concentration of 0.50 ± 0.27 μg/ml at 55 ± 29 hr after administration, with a harmonic mean terminal elimination half-life of 77.73 hr. Minimal levels of ciprofloxacin were detected after both oral and i.v. enrofloxacin administration, with concentrations below minimum inhibitory concentrations for most susceptible organisms. On the basis of the results of this study, enrofloxacin administered to American alligators at 5 mg/kg i.v. q 36 hr is expected to maintain plasma concentrations that approximate the minimum inhibitory concentration for susceptible organisms (0.5 μg/ml). Enrofloxacin administered to American alligators at 5 mg/kg p.o. is not expected to achieve minimum inhibitory values for susceptible organisms.}, number={3}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Helmick, KE and Papich, MG and Vliet, KA and Bennett, A and Bennett, RA and Jacobson, ER}, year={2004}, month={Sep}, pages={333–340} }
 @article{harms_papich_stamper_ross_rodriguez_hohn_2004, title={Pharmacokinetics of oxytetracycline in loggerhead sea turtles (Caretta caretta) after single intravenous and intramuscular injections}, volume={35}, ISSN={["1042-7260"]}, DOI={10.1638/03-083}, abstractNote={Abstract The pharmacokinetics of oxytetracycline in 2-yr-old loggerhead sea turtles (Caretta caretta) after single i.v. and i.m. injections were studied for biologic marking and therapeutic applications. Twenty juvenile turtles were divided into two treatment groups. Ten animals received 25 mg/kg of oxytetracycline i.v. and 10 received the same dosage i.m. Plasma oxytetracycline concentrations were analyzed by reverse-phase high-performance liquid chromatography. Data from the i.v. route best fit a three-compartment model, whereas noncompartmental analysis was used to compare data from both the i.v. and i.m routes. For the i.v. route, means for maximum plasma concentration, terminal phase half-life, systemic clearance, and apparent volume of distribution at steady state were 6.6 μg/ml, 66.1 hr, 290.7 ml/hr/kg, and 18.4 L, respectively. For the i.m. route, means for systemic availability, maximum plasma concentration, and elimination half-life were 91.8%, 1.6 μg/ml, and 61.9 hr, respectively. The remarkably high apparent volume of distribution may possibly be associated with a deep compartment of drug disposition such as bone deposition associated with the large skeletal mass of turtles and the fact that these were well-nourished, growing juveniles. Although maximum plasma concentration by i.m. administration was lower than for the i.v. route, the long elimination time indicates that an infrequent dosing interval may be effective for sensitive bacteria.}, number={4}, journal={JOURNAL OF ZOO AND WILDLIFE MEDICINE}, author={Harms, CA and Papich, MG and Stamper, A and Ross, PM and Rodriguez, MX and Hohn, AA}, year={2004}, month={Dec}, pages={477–488} }
 @article{kukanich_papich_2004, title={Pharmacokinetics of tramadol and the metabolite O-desmethyl tramadol in dogs}, volume={27}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2004.00578.x}, abstractNote={Tramadol is an analgesic and antitussive agent that is metabolized to O‐desmethyltramadol (M1), which is also active. Tramadol and M1 exert their mode of action through complex interactions between opiate, adrenergic, and serotonin receptors. The pharmacokinetics of tramadol and M1 were examined following intravenous and oral tramadol administration to six healthy dogs, as well as intravenous M1 to three healthy dogs. The calculated parameters for half‐life, volume of distribution, and total body clearance were 0.80 ± 0.12 h, 3.79 ± 0.93 L/kg, and 54.63 ± 8.19 mL/kg/min following 4.4 mg/kg tramadol HCl administered intravenously. The systemic availability was 65 ± 38% and half‐life 1.71 ± 0.12 h following tramadol 11 mg/kg p.o. M1 had a half‐life of 1.69 ± 0.45 and 2.18 ± 0.55 h following intravenous and oral administration of tramadol. Following intravenous M1 administration the half‐life, volume of distribution, and clearance of M1 were 0.94 ± 0.09 h, 2.80 ± 0.15 L/kg, and 34.93 ± 5.53 mL/kg/min respectively. Simulated oral dosing regimens at 5 mg/kg every 6 h and 2.5 mg/kg every 4 h predict tramadol and M1 plasma concentrations consistent with analgesia in humans; however, studies are needed to establish the safety and efficacy of these doses.}, number={4}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={KuKanich, B. and Papich, M.G.}, year={2004}, pages={1–8} }
 @article{kukanich_papich_2004, title={Plasma profile and pharmacokinetics of dextromethorphan after intravenous and oral administration in healthy dogs}, volume={27}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2004.00608.x}, abstractNote={Dextromethorphan is an N‐methyl‐d‐aspartate (NMDA) noncompetitive antagonist which has been used as an antitussive, analgesic adjunct, probe drug, experimentally to attenuate acute opiate and ethanol withdrawal, and as an anticonvulsant. A metabolite of dextromethorphan, dextrorphan, has been shown to behave pharmacodynamically in a similar manner to dextromethorphan. The pharmacokinetics of dextromethorphan were examined in six healthy dogs following intravenous (2.2 mg/kg) and oral (5 mg/kg) administration in a randomized crossover design. Dextromethorphan behaved in a similar manner to other NMDA antagonists upon injection causing muscle rigidity, ataxia to recumbency, sedation, urination, and ptyalism which resolved within 90 min. One dog repeatedly vomited upon oral administration and was excluded from oral analysis. Mean ± SD values for half‐life, apparent volume of distribution, and clearance after i.v. administration were 2.0 ±0.6 h, 5.1 ± 2.6 L/kg, and 33.8 ± 16.5 mL/min/kg. Oral bioavailability was 11% as calculated from naïve pooled data. Free dextrorphan was not detected in any plasma sample, however enzymatic treatment of plasma with glucuronidase released both dextromethorphan and dextrorphan indicating that conjugation is a metabolic route. The short half‐life, rapid clearance, and poor bioavailability of dextromethorphan limit its potential use as a chronic orally administered therapeutic.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={KuKanich, B and Papich, MG}, year={2004}, month={Oct}, pages={337–341} }
 @article{papich_2004, title={The relationship between susceptibility testing and efficacy}, journal={NAVC Clinician’s Brief}, author={Papich, M.G.}, year={2004}, month={Aug}, pages={45–47} }
 @article{martinez_papich_riviere_2004, title={Veterinary application of in vitro dissolution data and the Biopharmaceutics Classification System}, volume={30}, number={6}, journal={Stimuli to the Revision Process. Pharmacopeial Forum (United States Pharmacopeial Convention)}, author={Martinez, M.N. and Papich, M.G. and Riviere, J.E.}, year={2004}, pages={2–10} }
 @inbook{papich_2003, title={Antimicrobial Therapy for Horses}, ISBN={9780721695402}, url={http://dx.doi.org/10.1016/b978-0-7216-9540-2.50006-2}, DOI={10.1016/b978-0-7216-9540-2.50006-2}, booktitle={Current Therapy in Equine Medicine}, publisher={Elsevier}, author={Papich, M}, year={2003}, pages={6–11} }
 @article{papich_2003, title={Antimicrobial therapy for gastrointestinal diseases}, volume={19}, ISSN={0749-0739}, url={http://dx.doi.org/10.1016/j.cveq.2003.08.009}, DOI={10.1016/j.cveq.2003.08.009}, abstractNote={Antibiotics will always be needed in horses for many types of infections, but the adverse consequences also must be considered. For the conditions described in this article, there is justification for antibiotic therapy. The intestinal problems that antibiotics can induce are among the risks from their administration to horses. Disruption of the endogenous bacterial population, colitis, and diarrhea are the most common complications from antibiotic therapy.}, number={3}, journal={Veterinary Clinics of North America: Equine Practice}, publisher={Elsevier BV}, author={Papich, Mark G}, year={2003}, month={Dec}, pages={645–663} }
 @article{flammer_trogdon_papich_2003, title={Assessment of plasma concentrations of doxycycline in budgerigars fed medicated seed or water}, volume={223}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2003.223.993}, abstractNote={Abstract
				
					Objective—To determine whether plasma doxycycline
concentrations considered effective for treatment
of avian chlamydiosis could be safely established
and maintained in budgerigars via administration
of doxycycline in water or seed.
				
					Design—Prospective study.
				
					Animals—68 healthy mature budgerigars.
				
					Procedure—In 14-day trials, plasma doxycycline concentrations
were measured in budgerigars provided
with water containing 0, 50, 100, 200, or 400 mg of
doxycycline hyclate/L or a hulled seed diet containing 0,
100, 200, or 400 mg of doxycycline hyclate/kg. On the
basis of these results, birds were fed seed containing
300 mg of doxycycline/kg for 42 days, and a control
group received unmedicated seed. Blood samples for
plasma doxycycline analysis were collected either in
the morning on treatment days 4, 7, 14, 21, 28, 35, and
42 or in the afternoon on days 12, 26, and 40. Birds
were observed daily. On days 14, 28, and 42, physical
and plasma biochemical variables, PCV, and total solids
concentration were measured; cloacal specimens
were obtained for bacteriologic and fungal culture.
				
					Results—During a 14-day period, treatment with water
containing ≤ 400 mg of doxycycline/L did not maintain
plasma doxycycline concentrations of ≥ 1 μg/mL, but
seed containing 300 mg of doxycycline hyclate/kg maintained
mean plasma doxycycline concentrations > 0.98
μg/mL for 42 days without notable adverse effects.
				
					Conclusions and Clinical Relevance—Results suggest
that hulled seed containing 300 mg of doxycycline
hyclate/kg can safely establish and maintain
plasma doxycycline concentrations that are considered
adequate for treatment of chlamydiosis in adult
nonbreeding budgerigars. (J Am Vet Med Assoc 2003;
223:993–998)}, number={7}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Flammer, K and Trogdon, MM and Papich, M}, year={2003}, month={Oct}, pages={993–998} }
 @article{james_calle_raphael_papich_breheny_cook_2003, title={Comparison of Injectable Versus Oral Enrofloxacin Pharmacokinetics in Red-Eared Slider Thirties, Trachemys scripta elegans}, volume={13}, ISSN={1529-9651}, url={http://dx.doi.org/10.5818/1529-9651.13.1.5}, DOI={10.5818/1529-9651.13.1.5}, abstractNote={ABSTRACT Three male and three female red-eared slider turtles, Trachemys scripta elegans, were given an intramuscular (IM) injection of enrofloxacin (5 mg/kg body weight). Blood was obtained from a peripheral vein, and plasma concentrations of enrofloxacin and ciprofloxacin were measured at 0, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 hr post injection. After a period of six weeks, the same animals were given oral doses of enrofloxacin (10 mg/kg body weight). Blood was obtained and plasma concentrations of enrofloxacin and ciprofloxacin were measured at 1, 2, 5, 8, 12, 24, 36, 48, 72 hr post oral dosing. The highest mean concentrations of enrofloxacin and ciprofloxacin were 6.28 μg/ml 2 hr and 0.42 μg/ml 7.4 hr after IM injection and 3.44 μg/ml 5 hr and 0.35 μg/ml 6 hr after oral administration. The mean apparent elimination half-life of enrofloxacin was 17.6 hr after IM injection and 32.8 hr after oral administration. The half-life for ciprofloxacin was 28.4 hr post IM administration and 59.6 hr post-oral admi...}, number={1}, journal={Journal of Herpetological Medicine and Surgery}, publisher={Association of Reptilian and Amphibian Veterinarians (ARAV)}, author={James, Stephanie B. and Calle, Paul P. and Raphael, Bonnie L. and Papich, Mark and Breheny, James and Cook, Robert A.}, year={2003}, month={Jan}, pages={5–10} }
 @article{bidgood_papich_2003, title={Comparison of plasma and interstitial fluid concentrations of doxycycline and meropenem following constant rate intravenous infusion in dogs}, volume={64}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2003.64.1040}, abstractNote={AbstractObjective—To compare plasma (total and unbound) and interstitial fluid (ISF) concentrations of doxycycline and meropenem in dogs following constant rate IV infusion of each drug.Animals—6 adult Beagles.Procedure—Dogs were given a loading dose of doxycycline and meropenem followed by a constant rate IV infusion of each drug to maintain an 8-hour steady state concentration. Interstitial fluid was collected with an ultrafiltration device. Plasma and ISF were analyzed by high performance liquid chromatography. Protein binding and lipophilicity were determined. Plasma data were analyzed by use of compartmental methods.Results—Compared with meropenem, doxycycline had higher protein binding (11.87% [previously published value] vs 91.75 ± 0.63%) and lipophilicity (partition coefficients, 0.02 ± 0.01 vs 0.68 ± 0.05). A significant difference was found between ISF and plasma total doxycycline concentrations. No significant difference was found between ISF and plasma unbound doxycycline concentrations. Concentrations of meropenem in ISF and plasma (total and unbound) were similar. Plasma half-life, volume of distribution, and clearance were 4.56 ± 0.57 hours, 0.65 ± 0.82 L/kg, and 1.66 ± 2.21 mL/min/kg, respectively, for doxycycline and 0.73 ± 0.07 hours, 0.34 ± 0.06 L/kg, and 5.65 ± 2.76 mL/min/kg, respectively, for meropenem. The ISF half-life of doxycycline and meropenem was 4.94 ± 0.67 and 2.31 ± 0.36 hours, respectively.Conclusions and Clinical Relevance—The extent of protein binding determines distribution of doxycycline and meropenem into ISF. As a result of high protein binding, ISF doxycycline concentrations are lower than plasma total doxycycline concentrations. Concentrations of meropenem in ISF can be predicted from plasma total meropenem concentrations. (Am J Vet Res2003;64:1040–1046)}, number={8}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Bidgood, TL and Papich, MG}, year={2003}, month={Aug}, pages={1040–1046} }
 @article{hoppes_flammer_hoersch_papich_paul-murphy_2003, title={Disposition and analgesic cockatoos effects of fentanyl in white (Cacatua alba)}, volume={17}, ISSN={["1082-6742"]}, DOI={10.1647/2002-008}, abstractNote={Abstract Fentanyl is a mu opioid agonist with 80–100 times the analgesic potency of morphine. Fentanyl is used in several mammalian species for relief of severe pain, but its use has not been investigated in psittacine birds. To determine the pharmacologic disposition of fentanyl in healthy white cockatoos (Cacatua alba), we measured fentanyl plasma concentrations in sequentially collected samples after administration of fentanyl at 0.01 or 0.02 mg/kg IM. To investigate the analgesic effects of fentanyl in conscious cockatoos, we compared the change in pre- and posttreatment levels of electrical and thermal noxious stimuli necessary to elicit a withdrawal response in birds administered fentanyl at 2 different doses (0.02 mg/kg IM or 0.2 mg/kg SC) and those given saline. Fentanyl was rapidly absorbed and plasma concentrations declined with an elimination half-life of 1.2–1.4 hours. Plasma concentrations considered to be analgesic in humans were maintained for at least 2 hours with the 0.02 mg/kg dose. However, no significant difference was found in analgesic response between birds given saline and those given fentanyl at 0.02 mg/kg IM. Although the 0.2 mg/kg SC dose provided significant analgesia in some birds, fentanyl at this dose is not recommended as a routine analgesic agent because a large volume of drug must be injected and this dose causes hyperactivity in some birds.}, number={3}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Hoppes, S and Flammer, K and Hoersch, K and Papich, M and Paul-Murphy, J}, year={2003}, month={Sep}, pages={124–130} }
 @article{johansson_gardner_levine_papich_lafevers_fuquay_reagan_atkins_2003, title={Furosemide continuous rate infusion in the horse: Evaluation of enhanced efficacy and reduced side effects}, volume={17}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2003)017<0887:FCRIIT>2.3.CO;2}, abstractNote={Journal of Veterinary Internal MedicineVolume 17, Issue 6 p. 887-895 Open Access Furosemide Continuous Rate Infusion in the Horse: Evaluation of Enhanced Efficacy and Reduced Side Effects Anna M. Johansson, Anna M. Johansson Department of Clinical Sciences College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorSarah Y. Gardner, Corresponding Author Sarah Y. Gardner Department of Clinical Sciences College of Veterinary Medicine, North Carolina State University, Raleigh, NC DVM, PhD, Department of Clinical Sciences, College of Veterinary Medicine, Hillsborough Street 4700, Raleigh, NC 27606; e-mail: [email protected].Search for more papers by this authorJay F. Levine, Jay F. Levine Department of Farm Animal Health and Resource Management, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorMark G. Papich, Mark G. Papich Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorVirginia H. Reagan, Virginia H. Reagan Department of Clinical Sciences College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorClarke E. Atkins, Clarke E. Atkins Department of Clinical Sciences College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this author Anna M. Johansson, Anna M. Johansson Department of Clinical Sciences College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorSarah Y. Gardner, Corresponding Author Sarah Y. Gardner Department of Clinical Sciences College of Veterinary Medicine, North Carolina State University, Raleigh, NC DVM, PhD, Department of Clinical Sciences, College of Veterinary Medicine, Hillsborough Street 4700, Raleigh, NC 27606; e-mail: [email protected].Search for more papers by this authorJay F. Levine, Jay F. Levine Department of Farm Animal Health and Resource Management, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorMark G. Papich, Mark G. Papich Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorVirginia H. Reagan, Virginia H. Reagan Department of Clinical Sciences College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorClarke E. Atkins, Clarke E. Atkins Department of Clinical Sciences College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this author First published: 28 June 2008 https://doi.org/10.1111/j.1939-1676.2003.tb02529.xCitations: 32AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Abstract Continuous rate infusion (CRI) of furosemide in humans is considered superior to intermittent administration (IA). This study examined whether furosemide CRI, compared with IA, would increase diuretic efficacy with decreased fluid and electrolyte fluctuations and activation of the renin-angiotensin-aldosterone system (RAAS) in the horse. Five mares were used in a crossover-design study. During a 24-hour period, each horse received a total of 3 mg/kg furosemide by either CRI (0.12 mg/kg/h preceded by a loading dose of 0.12 mg/kg IV) or IA (1 mg/kg IV q8h). There was not a statistically significant difference in urine volume over 24 hours between methods; however, urine volume was significantly greater after CRI compared with IA during the first 8 hours ([median 25th percentile, 75th percentile]: 9.6 L [8.9, 14.4] for CRI versus 5.9 L [5.3, 6.0] for IA). CRI produced a more uniform urine flow, decreased fluctuations in plasma volume, and suppressed renal concentrating ability throughout the infusion period. Potassium, Ca, and Cl excretion was greater during CRI than IA (1,133 mmol [1,110, 1,229] versus 764 mmol [709, 904], 102.7 mmol [96.0, 117.2] versus 73.3 mmol [65.0, 73.5], and 1,776 mmol [1,657, 2,378] versus 1,596 mmol [1,457, 1,767], respectively). Elimination half-lives of furosemide were 1.35 and 0.47 hours for CRI and IA, respectively. The area under the excretion rate curve was 1,285.7 and 184.2 mL mg/mL for CRI and IA, respectively. Furosemide CRI (0.12 mg/kg/h) for 8 hours, preceded by a loading dose (0.12 mg/kg), is recommended when profound diuresis is needed acutely in horses. References 1 Jackson EK. Diuretics. In: JG Hardman, LE Limbird, PB Molinoff, RW Ruddon, AG Gilman, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. New York , NY : The McGraw-Hills Companies; 1995: 685–715. Web of Science®Google Scholar 2 Rose BD. Diuretics. Kidney Int 1991; 39: 336–352. 10.1038/ki.1991.43 CASPubMedWeb of Science®Google Scholar 3 Tobin T, Roberts BL, Swerczek TW, et al. The pharmacology of furosemide in the horse. III. Dose and time response relationships, effects of repeated dosing, and performance effects. J Equine Med Surg 1978; 2: 216–226. CASWeb of Science®Google Scholar 4 Hinchcliff KW, McKeever KH, Muir WW, 3rd. Furosemide-in-duced changes in plasma and blood volume of horses. J Vet Pharmacol Ther 1991; 14: 411–417. 10.1111/j.1365-2885.1991.tb00855.x CASPubMedWeb of Science®Google Scholar 5 Muir WW, McGuirk SM. Pharmacology and pharmacokinetics of drugs used to treat cardiac disease in horses. Vet Clin North Am Equine Pract 1985; 1: 335–352. 10.1016/S0749-0739(17)30759-9 CASPubMedWeb of Science®Google Scholar 6 Muir WW, Kohn CW, Sams R. Effects of furosemide on plasma volume and extracellular fluid volume in horses. Am J Vet Res 1978; 39: 1688–1691. CASPubMedWeb of Science®Google Scholar 7 Freestone JF, Carlson GP, Harrold DR, et al. Influence of furo-semide treatment on fluid and electrolyte balance in horses. Am J Vet Res 1988; 49: 1899–1902. CASPubMedWeb of Science®Google Scholar 8 Van Meyel JJ, Smits P, Russel FG, et al. Diuretic efficiency of furosemide during continuous administration versus bolus injection in healthy volunteers. Clin Pharmacol Ther 1992; 51: 440–444. 10.1038/clpt.1992.44 PubMedWeb of Science®Google Scholar 9 Lahav M, Regev A, Ra'anani P, et al. Intermittent administration of furosemide vs continuous infusion preceded by a loading dose for congestive heart failure. Chest 1992; 102: 725–731. 10.1378/chest.102.3.725 CASPubMedWeb of Science®Google Scholar 10 Acara MA. Renal pharmacology–Diuresis. In: CM Smith, AM Reynard, eds. Textbook of Pharmacology. Philadelphia , PA : WB Saunders Company; 1992: 554–588. Google Scholar 11 Baggot JD. The pharmacological basis of cardiac drug selection for use in horses. Equine Vet J Suppl 1995: 97–100. CASPubMedGoogle Scholar 12 Guthrie GP Jr, Cecil SG, Darden ED, et al. Dynamics of renin and aldosterone in the thoroughbred horse. Gen Comp Endocrinol 1982; 48: 296–299. 10.1016/0016-6480(82)90140-X CASPubMedWeb of Science®Google Scholar 13 Lee MG, Li T, Chiou WL. Effect of intravenous infusion time on the pharmacokinetics and pharmacodynamics of the same total dose of furosemide. Biopharm Drug Dispos 1986; 7: 537–547. 10.1002/bdd.2510070603 CASPubMedWeb of Science®Google Scholar 14 Pivac N, Rumboldt Z, Sardelic S, et al. Diuretic effects of fu-rosemide infusion versus bolus injection in congestive heart failure. Int J Clin Pharmacol Res 1998; 18: 121–128. CASPubMedWeb of Science®Google Scholar 15 Yelton SL, Gaylor MA, Murray KM. The role of continuous infusion loop diuretics. Ann Pharmacother 1995; 29: 1010–1014; quiz 1060–1011. 10.1177/106002809502901011 CASPubMedWeb of Science®Google Scholar 16 Gwilt PR. Pharmacokinetics. In: CR Craig, RE Stitzel, eds. Modern Pharmacology. Boston , MA : Little, Brown and Company; 1990: 68–81. Google Scholar 17 Chay S, Woods WE, Rowse K, et al. The pharmacology of furosemide in the horse. V. Pharmacokinetics and blood levels of fu-rosemide after intravenous administration. Drug Metab Dispos 1983; 11: 226–231. CASPubMedWeb of Science®Google Scholar 18 Harrison MH. Effects on thermal stress and exercise on blood volume in humans. Physiol Rev 1985; 65: 149–209. 10.1152/physrev.1985.65.1.149 CASPubMedWeb of Science®Google Scholar 19 Yamaoka K, Nakagawa T, Uno T. Application of Akaike's information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm 1978; 6: 165–175. 10.1007/BF01117450 CASPubMedWeb of Science®Google Scholar 20 Campbell MJ, Machin D. Non-parametric tests. In: MJ Campbell, D Machin, eds. Medical Statistics–A Commonsense Approach, 3rd ed. Chichester , UK : John Wiley & Sons Ltd; 1999: 163–165. Web of Science®Google Scholar 21 Chennavasin P, Seiwell R, Brater DC, et al. Pharmacodynamic analysis of the furosemide-probenecid interaction in man. Kidney Int 1979; 16: 187–195. 10.1038/ki.1979.120 CASPubMedWeb of Science®Google Scholar 22 Kaojarern S, Day B, Brater DC. The time course of delivery of furosemide into urine: An independent determinant of overall response. Kidney Int 1982; 22: 69–74. 10.1038/ki.1982.134 CASPubMedWeb of Science®Google Scholar 23 Hammarlund MM, Odlind B, Paalzow LK. Acute tolerance to furosemide diuresis in humans. Pharmacokinetic-pharmacodynamic modeling. J Pharmacol Exp Ther 1985; 233: 447–453. CASPubMedWeb of Science®Google Scholar 24 Streeten DH, Tomycz N, Anderson GH. Reliability of screening methods for the diagnosis of primary aldosteronism. Am J Med 1979; 67: 403–413. 10.1016/0002-9343(79)90786-1 CASPubMedWeb of Science®Google Scholar 25 Roberts BL, Blake JW, Tobin T. The pharmacology of furose-mide in the horse. II. Its detection, pharmacokinetics, and clearance from urine. J Equine Med Surg 1978; 2: 185–194. CASWeb of Science®Google Scholar Citing Literature Volume17, Issue6November 2003Pages 887-895 ReferencesRelatedInformation}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Johansson, AM and Gardner, SY and Levine, JF and Papich, MG and LaFevers, DH and Fuquay, LR and Reagan, VH and Atkins, CE}, year={2003}, pages={887–895} }
 @inbook{geor_papich_2003, edition={5th}, title={Once-daily Aminoglycoside Dosing Regimens}, booktitle={Current Therapy in Equine Medicine}, author={Geor, R.J. and Papich, M.G.}, editor={Robinson, N.E.Editor}, year={2003}, pages={850–853} }
 @article{stamper_papich_lewbart_may_plummer_stoskopf_2003, title={Pharmacokinetics of florfenicol in loggerhead sea turtles (Caretta caretta) after single intravenous and intramuscular injections}, volume={34}, DOI={10.1638/1042-7260(2003)34[0003:pofils]2.0.co;2}, abstractNote={Abstract The pharmocodynamics of single injections of florfenicol in yearling loggerhead sea turtles (Caretta caretta) were determined. Eight juvenile loggerhead sea turtles weighing 1.25 (±0.18) kg were divided into two groups. Four animals received 30 mg/kg of florfenicol i.v., and four received the same dose i.m. Plasma florfenicol concentrations were analyzed by reverse-phase high performance liquid chromatography. After the i.v. dose, there was a biphasic decline in plasma florfenicol concentration. The initial steep phase from 3 min to 1 hr had a half-life of 3 min, and there was a longer slow phase of elimination, with a half-life that ranged from 2 to 7.8 hr among turtles. The volume of distribution varied greatly and ranged from 10.46 to –60 L/kg. Clearance after the i.v. dose was 3.6–6.3 L/kg/hr. After the i.m. injection, there was a peak within 30 min of 1.4–5.6 μg/ml, and florfenicol was thereafter eliminated with a half-life of 3.2–4.3 hr. With either route, florfenicol plasma concentrations were below the minimum inhibitory concentrations for sensitive bacteria within 1 hr. Florfenicol does not appear to be a practical antibiotic in sea turtles when administered at these doses.}, number={1}, journal={Journal of Zoo and Wildlife Medicine}, author={Stamper, M. A. and Papich, Mark and Lewbart, Gregory and May, S. B. and Plummer, D. D. and Stoskopf, M. K.}, year={2003}, pages={3–8} }
 @article{simpson_papich_2003, title={Pharmacologic management in veterinary behavioral medicine}, volume={33}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/s0195-5616(02)00130-4}, DOI={10.1016/S0195-5616(02)00130-4}, abstractNote={As our knowledge expands, behavioral pharmacology plays an increasingly important role in behavioral medicine. Drugs traditionally categorized as anxiolytics, antidepressants, anticonvulsants, and hormones may be used to help manage a range of animal behavioral problems. Knowledge of how these agents act in the body and interact with other agents is imperative for safe and efficacious use.}, number={2}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Simpson, Barbara Sherman and Papich, Mark G.}, year={2003}, month={Mar}, pages={365–404} }
 @article{bermingham_papich_2002, title={Pharmacokinetics after intravenous and oral administration of enrofloxacin in sheep}, volume={63}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2002.63.1012}, abstractNote={AbstractObjective—To compare pharmacokinetics of enrofloxacin administered IV and in various oral preparations to ewes.Animals—5 mature Katahdin ewes weighing 42 to 50 kg.Procedure—Ewes received 4 single-dose treatments of enrofloxacin in a nonrandomized crossover design followed by a multiple-dose oral regimen. Single-dose treatments consisted of an IV bolus of enrofloxacin (5 mg/kg), an oral drench (10 mg/kg) made from crushed enrofloxacin tablets, oral administration in feed (10 mg/kg; mixture of crushed enrofloxacin tablets and grain), and another type of oral administration in feed (10 mg/kg; mixture of enrofloxacin solution and grain). The multiple-dose regimen consisted of feeding a mixture of enrofloxacin solution and grain (10 mg/kg, q 24 h, for 7 days). Plasma concentrations of enrofloxacin and ciprofloxacin were measured by use of high-performance liquid chromatography.Results—Harmonic mean half-life for oral administration was 14.80, 10.80, and 13.07 hours, respectively, for the oral drench, crushed tablets in grain, and enrofloxacin solution in grain. Oral bioavailability for the oral drench, crushed tablets in grain, and enrofloxacin in grain was 47.89, 98.07, and 94.60%, respectively, and median maximum concentration (Cmax) was 1.61, 2.69, and 2.26 µg/ml, respectively. Median Cmaxof the multiple-dose regimen was 2.99 µg/ml.Conclusions and Clinical Relevance—Enrofloxacin administered orally to sheep has a prolonged half-life and high oral bioavailability. Oral administration at 10 mg/kg, q 24 h, was sufficient to achieve a plasma concentration of 8 to 10 times the minimum inhibitory concentration (MIC) of any microorganism with an MIC ≤ 0.29 µg/ml. (Am J Vet Res2002; 63:1012–1017)}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Bermingham, EC and Papich, MG}, year={2002}, month={Jul}, pages={1012–1017} }
 @article{papich_van camp_cole_whitacre_2002, title={Pharmacokinetics and endometrial tissue concentrations of enrofloxacin and the metabolite ciprofloxacin after i.v. administration of enrofloxacin to mares}, volume={25}, ISSN={["1365-2885"]}, DOI={10.1046/j.1365-2885.2002.00434.x}, abstractNote={Enrofloxacin was administered i.v. to five adult mares at a dose of 5 mg/kg. After administration, blood and endometrial biopsy samples were collected at regular intervals for 24 h. The plasma and tissue samples were analyzed for enrofloxacin and the metabolite ciprofloxacin by high‐pressure liquid chromatography. In plasma, enrofloxacin had a terminal half‐life (t½), volume of distribution (area method), and systemic clearance of 6.7 ± 2.9 h, 1.9 ± 0.4 L/kg, and 3.7 ± 1.4 mL/kg/min, respectively. Ciprofloxacin had a maximum plasma concentration (Cmax) of 0.28 ± 0.09 μg/mL. In endometrial tissue, the enrofloxacin Cmax was 1.7 ± 0.5 μg/g, and the t½ was 7.8 ± 3.7 h. Ciprofloxacin Cmax in tissues was 0.15 ± 0.04 μg/g and the t½ was 5.2 ± 2.0 h. The tissue:plasma enrofloxacin concentration ratios (w/w:w/v) were 0.175 ± 0.08 and 0.47 ± 0.06 for Cmax and AUC, respectively. For ciprofloxacin, these values were 0.55 ± 0.13 and 0.58 ± 0.31, respectively. We concluded that plasma concentrations achieved after 5 mg/kg i.v. are high enough to meet surrogate markers for antibacterial activity (Cmax:MIC ratio, and AUC:MIC ratio) considered effective for most susceptible gram‐negative bacteria. Endometrial tissue concentrations taken from the mares after dosing showed that enrofloxacin and ciprofloxacin both penetrate this tissue adequately after systemic administration and would attain concentrations high enough in the tissue fluids to treat infections of the endometrium caused by susceptible bacteria.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Papich, MG and Van Camp, SD and Cole, JA and Whitacre, MD}, year={2002}, month={Oct}, pages={343–350} }
 @article{davis_gardner_jones_schwabenton_papich_2002, title={Pharmacokinetics of azithromycin in foals after i.v. and oral dose and disposition into phagocytes}, volume={25}, ISSN={["1365-2885"]}, url={http://europepmc.org/abstract/med/12000529}, DOI={10.1046/j.1365-2885.2002.00387.x}, abstractNote={The properties of azithromycin suggest that it may be an alternative to erythromycin for treatment of Rhodococcus equi pneumonia in foals. To investigate this possibility, the disposition of azithromycin in plasma, polymorphonuclear leukocytes (PMN), and alveolar cells was examined after a single administration in foals. Azithromycin suspension was administered orally (p.o.) at a dose of 10 mg/kg to five healthy 2–3‐month‐old foals. Two weeks later, azithromycin for injection was administered by intravenous (i.v.) infusion at a dose of 5 mg/kg to the same foals. Plasma samples were collected after p.o. and i.v. administration. Peripheral blood PMN and bronchoalveolar lavage fluid and alveolar cells were collected after p.o. administration. Azithromycin concentrations were determined by reverse‐phase high‐performance liquid chromatography (HPLC) with coulometric electrochemical detection. Azithromycin p.o. absorption was variable with a mean systemic availability of 39% (±20%). The plasma half‐life was 16 and 18.3 h after i.v. and p.o. administration, respectively. Azithromycin had a very large volume of distribution (Vd) of 11.6 L/kg [Vd(ss)] and 12.4 L/kg [Vd(area)]. The large Vd can be attributed to high tissue and intracellular concentrations, exhibited by the high concentration of azithromycin in PMN and alveolar cells. The PMN half‐life was 49.2 h. Dosage of 10 mg/kg of azithromycin p.o. once daily for foals with R. equi pneumonia is recommended for further study.}, number={2}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Davis, JL and Gardner, SY and Jones, SL and Schwabenton, BA and Papich, MG}, year={2002}, month={Apr}, pages={99–104} }
 @article{mallo_harms_lewbart_papich_2002, title={Pharmacokinetics of fluconazole in loggerhead sea turtles (Caretta caretta) after single intravenous and subcutaneous injections, and multiple subcutaneous injections}, volume={33}, DOI={10.1638/1042-7260(2002)033[0029:pofils]2.0.co;2}, abstractNote={Abstract Superficial and systemic mycotic infections are common among clinically ill sea turtles, which places growing importance on the establishment of pharmacokinetic-based dosage regimens for antifungal drugs. The pharmacokinetic properties of the antifungal drug fluconazole, after intravenous (i.v.) and subcutaneous (s.c.) injections, were studied in juvenile loggerhead sea turtles (Caretta caretta) housed at 23.0–26.5°C. Fluconazole pharmacokinetic properties were further assessed in a multiple-dose s.c. regimen derived from the pharmacokinetic parameters determined in the single-dose study. Pharmacokinetic parameters were calculated, using a two-compartment model, from plasma concentration–time data obtained after single i.v. and s.c. administrations of fluconazole at a dosage of 2.5 mg/kg body weight in six juvenile sea turtles. Blood samples were collected at intervals through 120 hr after each dose, and the concentration of fluconazole in plasma was measured by reverse-phase high-performance liquid chromatography. The i.v. and s.c. elimination half-lives were 139.5 ± 36.0 and 132.6 ± 48.7 hr (mean ± SD), respectively. Systemic clearance of fluconazole was 8.2 ± 4.3 ml/kg·hr, and the apparent volume of distribution at steady state was 1.38 ± 0.29 L/kg. A multiple-dose regimen was derived, which consisted of a loading dose of 21 mg/kg body weight and subsequent doses of 10 mg/kg administered through s.c. injection every 120 hr (5 days). This regimen was administered to four juvenile sea turtles for 10 days, and blood samples were taken to determine peak and trough plasma concentrations of fluconazole. The mean concentrations for the two peak concentrations were 16.9 ± 1.1 and 19.1 ± 2.8 μg/ml 4 hr after dosing, and the mean concentrations for the three trough concentrations were 7.2 ± 2.2, 10.4 ± 2.7, and 10.7 ± 2.9 μg/ml 120 hr after dosing. The terminal half-life after the last dose was calculated at 143 hr. Throughout the multiple dosing, fluconazole concentrations remained above approximately 8 μg/ml, a concentration targeted when treating mycotic infections in humans. The results of this study suggest that fluconazole can be effectively administered to sea turtles at a dosage of 10 mg/kg every 5 days after a loading dose of 21 mg/kg.}, number={1}, journal={Journal of Zoo and Wildlife Medicine}, author={Mallo, K. M. and Harms, C. A. and Lewbart, Gregory and Papich, Mark}, year={2002}, pages={29–35} }
 @article{bidgood_papich_2002, title={Plasma pharmacokinetics and tissue fluid concentrations of meropenem after intravenous and subcutaneous administration in dogs}, volume={63}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2002.63.1622}, abstractNote={Abstract
				
					Objective—To estimate pharmacokinetic variables
and measure tissue fluid concentrations of meropenem
after IV and SC administration in dogs.
				
					Animals—6 healthy adult dogs.
				
					Procedure—Dogs were administered a single dose
of meropenem (20 mg/kg) IV and SC in a crossover
design. To characterize the distribution of meropenem
in dogs and to evaluate a unique tissue fluid collection
method, an in vivo ultrafiltration device was used to
collect interstitial fluid. Plasma, tissue fluid, and urine
samples were analyzed by use of high-performance
liquid chromatography. Protein binding was determined
by use of an ultrafiltration device.
				
					Results—Plasma data were analyzed by compartmental
and noncompartmental pharmacokinetic
methods. Mean ± SD values for half-life, volume of
distribution, and clearance after IV administration for
plasma samples were 0.67 ± 0.07 hours, 0.372 ±
0.053 L/kg, and 6.53 ± 1.51 mL/min/kg, respectively,
and half-life for tissue fluid samples was 1.15 ± 0.57
hours. Half-life after SC administration was 0.98 ±
0.21 and 1.31 ± 0.54 hours for plasma and tissue fluid,
respectively. Protein binding was 11.87%, and
bioavailability after SC administration was 84%.
				
					Conclusions and Clinical Relevance—Analysis of
our data revealed that tissue fluid and plasma
(unbound fraction) concentrations were similar.
Because of the kinetic similarity of meropenem in the
extravascular and vascular spaces, tissue fluid concentrations
can be predicted from plasma concentrations.
We concluded that a dosage of 8 mg/kg, SC,
every 12 hours would achieve adequate tissue fluid
and urine concentrations for susceptible bacteria with
a minimum inhibitory concentration of 0.12 µg/mL.
(Am J Vet Res 2002;63:1622–1628)}, number={12}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Bidgood, T and Papich, MG}, year={2002}, month={Dec}, pages={1622–1628} }
 @article{white_carlotti_pin_bonenberger_ihrke_monet_nishifuji_iwasaki_papich_2002, title={Putative drug-related pemphigus foliaceus in four dogs}, volume={13}, ISSN={["1365-3164"]}, DOI={10.1046/j.1365-3164.2002.00297.x}, abstractNote={Abstract Four dogs developed cutaneous lesions following the administration of various antibiotics. Histopathology of the lesions was compatible with pemphigus foliaceus, although apoptotic cells suggestive of erythema multiforme were seen in two cases. In two dogs the lesions resolved after 7.5–8.5 months of immune‐suppressive treatment. No recurrence was seen during the follow‐up period (3 and 4.5 years). The lesions in the other two dogs resolved within 3 weeks to 3 months following discontinuation of the antibiotic. No recurrence of clinical signs occurred during the follow‐up period (1 and 4 years, respectively).}, number={4}, journal={VETERINARY DERMATOLOGY}, author={White, SD and Carlotti, DN and Pin, D and Bonenberger, T and Ihrke, PJ and Monet, E and Nishifuji, K and Iwasaki, T and Papich, MG}, year={2002}, month={Aug}, pages={195–202} }
 @book{papich_2002, place={Philadelphia, PA}, edition={1st}, title={Saunders Handbook of Veterinary Drugs}, publisher={Saunders}, author={Papich, M.G.}, year={2002} }
 @article{hopwood_gookin_papich_2001, title={Adverse reactions to sulfonamide administration}, volume={3}, number={4}, journal={Compendium for Continuing Education for the Practicing Veterinarian}, author={Hopwood, R.M. and Gookin, J.L. and Papich, M.G.}, year={2001}, pages={5–12} }
 @inbook{heit_papich_riviere_2001, title={Antifungal and antiviral drugs}, ISBN={0813817439}, booktitle={Veterinary Pharmacology: Therapeutics (8th ed.)}, publisher={Ames, IA: Iowa State University Press}, author={Heit, M. C. and Papich, M. G. and Riviere, J. E.}, year={2001}, pages={918–946} }
 @inbook{papich_riviere_2001, title={Chloramphenicol and derivatives, macrolides, lincosamides, and miscellaneous antibiotics}, ISBN={0813817439}, booktitle={Veterinary pharmacology and therapeutics (8th ed.)}, publisher={Ames, IA: Iowa State University Press}, author={Papich, M. G. and Riviere, J. E.}, year={2001}, pages={868–897} }
 @article{gardner_papich_2001, title={Comparison of cefepime pharmacokinetics in neonatal foals and adult dogs}, volume={24}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1046/j.1365-2885.2001.00326.x}, DOI={10.1046/j.1365-2885.2001.00326.x}, abstractNote={The pharmacokinetics of cefepime, a new fourth generation cephalosporin with enhanced antibacterial activity, was examined in neonatal foals and adult dogs. Cefepime was administered intravenously (i.v.) at a dose of 14 mg/kg to five neonatal foals and six adult dogs. Blood samples were collected in both groups of animals and plasma cefepime concentrations measured by reverse‐phase high‐performance liquid chromatography (HPLC). Cefepime concentrations in both groups of animals were described by a two‐compartment pharmacokinetic model with elimination half‐lives of 1.65 and 1.09 h for the foal and dog, respectively. We tested whether or not pharmacokinetic parameters for cefepime could be scaled across species using principles of allometry. The parameters of elimination half‐life (t½β), apparent volume of distribution (VDarea), and systemic clearance (CL) were scaled linearly to body weight on a double logarithmic plot with allometric exponents for body weight of 0.26, 1.08 and 0.72, respectively. This study further determined doses for cefepime, a potentially useful antibiotic for neonatal foals and dogs, from the pharmacokinetic values. An i.v. dose of cefepime estimated from this study for treating sensitive bacteria was 11 mg/kg every 8 h for neonatal foals and 40 mg/kg every 6 h for dogs.}, number={3}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Gardner, S. Y. and Papich, M. G.}, year={2001}, month={Jun}, pages={187–192} }
 @article{gookin_levy_law_papich_poore_breitschwerdt_2001, title={Experimental infection of cats with Tritrichomonas foetus}, volume={62}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.2001.62.1690}, DOI={10.2460/ajvr.2001.62.1690}, abstractNote={AbstractObjective—To determine whether infection withTritrichomonas foetuscauses diarrhea in specific pathogen-free orCryptosporidiumcoinfected cats.Animals—4 cats with subclinical cryptosporidiosis (group 1) and 4 specific-pathogen-free cats (group 2).Procedure—Cats were infected orogastrically with an axenic culture ofT foetusisolated from a kitten with diarrhea. Direct microscopy and protozoal culture of feces, fecal character, serial colonic mucosal biopsy specimens, and response to treatment with nitazoxanide (NTZ; group 1) or prednisolone (groups 1 and 2) were assessed.Results—Infection withT foetuspersisted in all cats for the entire 203-day study and resulted in diarrhea that resolved after 7 weeks. Group-1 cats had an earlier onset, more severe diarrhea, and increased number of trichomonads on direct fecal examination, compared with group-2 cats. Use of NTZ eliminated shedding ofT foetusandCryptosporidiumoocysts, but diarrhea consisting of trichomonad-containing feces recurred when treatment was discontinued. Prednisolone did not have an effect on infection withT foetusbut resulted in reappearance ofCryptosporidiumoocysts in the feces of 2 of 4 cats. During necropsy,T foetuswas isolated from contents of the ileum, cecum, and colon.Tritrichomonas foetusorganisms and antigen were detected on surface epithelia and within superficial detritus of the cecal and colonic mucosa.Conclusions and Clinical Relevance—After experimental inoculation in cats,T foetusorganisms colonize the ileum, cecum, and colon, reside in close contact with the epithelium, and are associated with transient diarrhea that is exacerbated by coexisting cryptosporidiosis but not treatment with prednisolone. (Am J Vet Res2001;62:1690–1697)}, number={11}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Gookin, Jody L. and Levy, Michael G. and Law, J. Mac and Papich, Mark G. and Poore, Matthew F. and Breitschwerdt, Edward B.}, year={2001}, month={Nov}, pages={1690–1697} }
 @inbook{papich_riviere_2001, title={Fluoroquinolones antimicrobial drugs}, volume={45}, ISBN={0813817439}, booktitle={Veterinary pharmacology and therapeutics (8th ed.)}, publisher={Ames, IA: Iowa State University Press}, author={Papich, M. G. and Riviere, J. E.}, year={2001}, pages={898–917} }
 @article{sellon_monroe_roberts_papich_2001, title={Pharmacokinetics and adverse effects of butorphanol administered by single intravenous injection or continuous intravenous infusion in horses}, volume={62}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2001.62.183}, abstractNote={Abstract
				
					Objective—To determine an infusion rate of butorphanol
tartrate in horses that would maintain therapeutic
plasma drug concentrations while minimizing
development of adverse behavioral and gastrointestinal
tract effects.
				
					Animals—10 healthy adult horses.
				
					Procedure—Plasma butorphanol concentrations
were determined by use of high-performance liquid
chromatography following administration of butorphanol
by single IV injection (0.1 to 0.13 mg/kg of
body weight) or continuous IV infusion (loading dose,
17.8 µg/kg; infusion dosage, 23.7 µg/kg/h for 24
hours). Pharmacokinetic variables were calculated,
and changes in physical examination data, gastrointestinal
tract transit time, and behavior were determined
over time.
				
					Results—A single IV injection of butorphanol was
associated with adverse behavioral and gastrointestinal
tract effects including ataxia, decreased borborygmi,
and decreased defecation. Elimination half-life of
butorphanol was brief (44.37 minutes). Adverse gastrointestinal
tract effects were less apparent during
continuous 24-hour infusion of butorphanol at a
dosage that resulted in a mean plasma concentration
of 29 ng/ml, compared with effects after a single IV
injection. No adverse behavioral effects were
observed during or after continuous infusion.
				
					Conclusions and Clinical Relevance—Continuous
IV infusion of butorphanol for 24 hours maintained
plasma butorphanol concentrations within a range
associated with analgesia. Adverse behavioral and
gastrointestinal tract effects were minimized during
infusion, compared with a single injection of butorphanol.
Continuous infusion of butorphanol may be a
useful treatment to induce analgesia in horses. (Am J
Vet Res 2001;62:183–189)}, number={2}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Sellon, DC and Monroe, VL and Roberts, MC and Papich, MG}, year={2001}, month={Feb}, pages={183–189} }
 @article{latimer_colitz_campbell_papich_2001, title={Pharmacokinetics of fluconazole following intravenous and oral administration and body fluid concentrations of fluconazole following repeated oral dosing in horses}, volume={62}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.2001.62.1606}, abstractNote={AbstractObjective—To determine the pharmacokinetics of fluconazole in horses.Animals—6 clinically normal adult horses.Procedure—Fluconazole (10 mg/kg of body weight) was administered intravenously or orally with 2 weeks between treatments. Plasma fluconazole concentrations were determined prior to and 10, 20, 30, 40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after administration. A long-term oral dosing regimen was designed in which all horses received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24 hours for 10 days. Fluconazole concentrations were determined in aqueous humor, plasma, CSF, synovial fluid, and urine after administration of the final dose.Results—Mean (± SD) apparent volume of distribution of fluconazole at steady state was 1.21 ± 0.01 L/kg. Systemic availability and time to maximum plasma concentration following oral administration were 101.24 ± 27.50% and 1.97 ± 1.68 hours, respectively. Maximum plasma concentrations and terminal halflives after IV and oral administration were similar. Plasma, CSF, synovial fluid, aqueous humor, and urine concentrations of fluconazole after long-term oral administration of fluconazole were 30.50 ± 23.88, 14.99 ± 1.86, 14.19 ± 5.07, 11.39 ± 2.83, and 56.99 ± 32.87 µg/ml, respectively.Conclusion and Clinical Relevance—Bioavailability of fluconazole was high after oral administration to horses. Long-term oral administration maintained plasma and body fluid concentrations of fluconazole above the mean inhibitory concentration (8.0 mg/ml) reported for fungal pathogens in horses. Fluconazole may be an appropriate agent for treatment of fungal infections in horses. (Am J Vet Res2001;62:1606–1611).}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Latimer, FG and Colitz, CMH and Campbell, NB and Papich, MG}, year={2001}, month={Oct}, pages={1606–1611} }
 @article{flammer_whitt-smith_papich_2001, title={Plasma concentrations of doxycycline in selected psittacine birds when administered in water for potential treatment of Chlamydophila psittaci infection}, volume={15}, ISSN={["1082-6742"]}, DOI={10.1647/1082-6742(2001)015[0276:PCODIS]2.0.CO;2}, abstractNote={Abstract Infection by Chlamydophila psittaci (formerly Chlamydia psittaci) is a common cause of morbidity and mortality in companion psittacine birds and is transmissible to humans. Replication of Chlamydophila is inhibited by plasma doxycycline concentrations greater than 1 μg/ml, but prolonged treatment periods of 30–45 days are needed to eliminate infection. Medication of birds for this prolonged period is difficult with current treatment methods. In this study, drinking water medicated with doxycycline hyclate at 800 mg/L was provided ad libitum to healthy African grey parrots (Psittacus erithacus timneh) and Goffin's cockatoos (Cacatua goffini) for 42 days. Blood samples for doxycycline analysis were collected on treatment days 4, 7, 14, 21, 28, 35, and 42. Mean doxycycline concentrations exceeded 1 μg/ml throughout the 42-day treatment period. In the African grey parrots, the mean doxycycline concentration (± SD) for all plasma samples collected during the study was 1.51 ± 0.68 μg/ml and doxycycline concentrations were greater than 1 μg/ml in 73% of the samples. In the Goffin's cockatoos, the overall mean was 2.78 ± 1.00 μg/ml and doxycycline concentrations exceeded 1 μg/ml in all samples. No adverse effects were noted in the African grey parrots. All of the 8 treated Goffin's cockatoos were physically healthy, but changes in plasma biochemical analyses suggested mild hepatic damage in 3 birds. Results of plasma biochemical analyses in these cockatoos were within reference ranges when retested 7 days after doxycycline treatment ended. The results of this study suggest that doxycycline-medicated water can safely maintain plasma concentrations adequate for treating avian Chlamydophila infections in African grey parrots and Goffin's cockatoos housed under standardized conditions.}, number={4}, journal={JOURNAL OF AVIAN MEDICINE AND SURGERY}, author={Flammer, K and Whitt-Smith, D and Papich, M}, year={2001}, month={Dec}, pages={276–282} }
 @misc{riviere_papich_2001, title={Potential and problems of developing transdermal patches for veterinary applications}, volume={50}, ISSN={["1872-8294"]}, DOI={10.1016/S0169-409X(01)00157-0}, abstractNote={A new frontier in the administration of therapeutic drugs to veterinary species is transdermal drug delivery. The primary challenge in developing these systems is rooted in the wide differences in skin structure and function seen in species ranging from cats to cows. The efficacy of a transdermal system is primarily dependent upon the barrier properties of the targeted species skin, as well as the ratio of the area of the transdermal patch to the species total body mass needed to achieve effective systemic drug concentrations. A drug must have sufficient lipid solubility to traverse the epidermal barrier to be considered for delivery for this route. A number of insecticides have been developed in liquid "pour-on" formulations that illustrate the efficacy of this route of administration for veterinary species. The human transdermal fentanyl patch has been successfully used in cats and dogs for post-operative analgesia. The future development of transdermal drug delivery systems for veterinary species will be drug and species specific. With efficient experimental designs and available transdermal patch technology, there are no obvious hurdles to the development of effective systems in many veterinary species.}, number={3}, journal={ADVANCED DRUG DELIVERY REVIEWS}, author={Riviere, JE and Papich, MG}, year={2001}, month={Sep}, pages={175–203} }
 @article{levy_crawford_collante_papich_2001, title={Use of adult cat serum to correct failure of passive transfer in kittens}, volume={219}, DOI={10.2460/javma.2001.219.1401}, abstractNote={AbstractObjective—To evaluate the use of adult cat serum as an immunoglobulin supplement in kittens with failure of passive transfer.Design—Randomized controlled study.Animals—11 specific pathogen-free queens and their 43 kittens.Procedure—Kittens were removed from the queens at birth, prior to suckling colostrum, and randomly assigned to 1 of 4 groups: colostrum-deprived, colostrum-fed, colostrum-deprived and administration of pooled adult cat serum IP, and colostrum-deprived and administration of pooled adult serum SC. Colostrum-fed kittens were returned to the queen and allowed to suckle normally. Colostrum-deprived kittens were isolated from the queen and fed a kitten milk replacer for 2 days to prevent absorption of colostral IgG. All colostrum-deprived kittens were returned to the queen on day 3. Serum IgG concentrations were measured by radial immunodiffusion in the kittens at birth and 2 days and 1, 2, 4, 6, and 8 weeks after birth.Results—None of the kittens had detectable serum IgG at birth. Both IP and SC administration of adult cat serum resulted in peak serum IgG concentrations equivalent to those in kittens that suckled normally. Untreated colostrum-deprived kittens did not achieve serum IgG concentrations comparable to those for kittens in the other groups until 6 weeks of age.Conclusions and Clinical Relevance—Results suggest that adult cat serum may be used as an immunoglobulin supplement in colostrum-deprived kittens. Although the minimum concentration of IgG necessary to protect kittens from infection is unknown, concentrations achieved were comparable to those in kittens that suckled normally. (J Am Vet Med Assoc2001;219:1401–1405)}, number={10}, journal={Journal of the American Veterinary Medical Association}, author={Levy, J. K. and Crawford, P. C. and Collante, W. R. and Papich, Mark}, year={2001}, pages={1401–1405} }
 @article{van camp_papich_whitacre_2000, title={Administration of ticarcillin in combination with clavulanic acid intravenously and intrauterinely to clinically normal oestrous mares}, volume={23}, ISSN={["1365-2885"]}, DOI={10.1046/j.1365-2885.2000.00297.x}, abstractNote={Ticarcillin and clavulanic acid (potassium clavulanate) were administered to normal oestrous mares intravenously (i.v.) at a dose of 50 and 1.67 mg/kg for ticarcillin and clavulanate, respectively. In a crossover design, the same drugs were administered intrauterine (i.u.) at a dose of 12.4 and 0.4 mg/kg for ticarcillin and clavulanate, respectively. The i.u. dose was administered in 100 mL of saline solution. Endometrial tissue biopsies and plasma samples were collected after drug administration for the determination of ticarcillin and clavulanate concentrations by high-pressure liquid chromatography and pharmacokinetic calculations. After i.u. administration both drugs were poorly absorbed into the plasma. The ticarcillin half-life from tissue and plasma was short after i.v. administration. Although concentrations in tissue were higher after i.u. administration than i.v., concentrations of ticarcillin declined rapidly, which would necessitate frequent treatment in order to maintain drug concentrations above the minimum inhibitory concentrations (MIC) throughout the treatment period. Clavulanate concentrations in tissue were either low or persisted for only a short time after administration via either route. It appears that addition of clavulanate to the formulation for treatment of i.u. infections in mares is of questionable value based on these concentrations.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Van Camp, SD and Papich, MG and Whitacre, MD}, year={2000}, month={Dec}, pages={373–378} }
 @article{gulland_stoskopf_johnson_riviere_papich_2000, title={Amoxicillin pharmacokinetics in harbor seals (Phoca vitulina) and northern elephant seals (Mirounga angustirostris) following single dose intravenous administration: implications for interspecific dose sealing}, volume={23}, ISSN={["0140-7783"]}, DOI={10.1046/j.1365-2885.2000.00263.x}, abstractNote={The pharmacokinetics of sodium amoxicillin after a single intravenous dose of 20 mg/kg were determined in ten harbor seals (Phoca vitulina) and ten northern elephant seals (Mirounga angustirostris). The seals ranged in age from 1 to 6 months and the mean weights were 11.7 kg (range, 9.5–18.5 kg) for harbor seals and 47.1 kg (range, 39.5–61.4 kg) for elephant seals. The median half‐life of amoxicillin (quartiles) in harbor seals, 1.5 (1.0–3.1) h, was not statistically different from that of elephant seals, 2.0 (1.4–3.8) h, nor were the differences between the terminal elimination rate constants between the two species. The only statistically significant differences between species were for area‐under‐the‐curve (AUC), and total systemic clearance. The lack of statistical significance for differences in the volume of distribution at steady‐state (Vss) may have been due to minor differences in the time frame of data collection and dose administered between the two groups. A true physiologic difference in drug handling, possibly related to renal perfusion or tubal secretory efficiency could affect amoxicillin kinetics in these species, and longer administration intervals may be appropriate for elephant seals as compared to harbor seals when administering multiple dose amoxicillin therapy at 20 mg/kg.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Gulland, FM and Stoskopf, MK and Johnson, SP and Riviere, J and Papich, MG}, year={2000}, month={Aug}, pages={223–228} }
 @article{de jaham_paradis_papich_2000, title={Antifungal dermatologic agents: Azoles and allylamines}, volume={22}, number={6}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={De Jaham, C. and Paradis, M. and Papich, M.G.}, year={2000}, pages={548–559} }
 @inbook{papich_2000, place={Philadelphia}, edition={13th}, title={Antihistamines: current therapeutic use}, ISBN={0721655238}, booktitle={Kirk's Current Veterinary Therapy}, publisher={W.B. Saunders Company}, author={Papich, M.G.}, editor={Bonagura, J.D.Editor}, year={2000}, pages={48–53} }
 @inbook{papich_2000, place={Philadelphia}, edition={5th}, title={Antimicrobial drugs}, booktitle={Textbook of Veterinary Internal Medicine}, publisher={W.B. Saunders Company}, author={Papich, M.G.}, editor={Ettinger, S.J. and Feldman, E.C.Editors}, year={2000}, pages={301–307} }
 @inbook{papich_2000, place={Philadelphia}, edition={13th}, title={Bacterial resistance}, ISBN={0721655238}, booktitle={Kirk's Current Veterinary Therapy}, publisher={W.B. Saunders Company}, author={Papich, M.G.}, editor={Bonagura, J.D.Editor}, year={2000}, pages={262–267} }
 @article{lee_papich_hardie_2000, title={Comparison of pharmacokinetics of fentanyl after intravenous and transdermal administration in cats}, volume={61}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2000.61.672}, abstractNote={AbstractObjective—To compare pharmacokinetic and pharmacodynamic characteristics of fentanyl citrate after IV or transdermal administration in cats.Animals—6 healthy adult cats with a mean weight of 3.78 kg.Procedure—Each cat was given fentanyl IV (25 mg/cat; mean ± SD dosage, 7.19 ± 1.17 mg/kg of body weight) and via a transdermal patch (25 µg of fentanyl/h). Plasma concentrations of fentanyl were measured by use of radioimmunoassay. Pharmacokinetic analyses of plasma drug concentrations were conducted, using an automated curvestripping process followed by nonlinear, leastsquares regression. Transdermal delivery of drug was calculated by use of IV pharmacokinetic data.Results—Plasma concentrations of fentanyl given IV decreased rapidly (mean elimination half-life, 2.35 ± 0.57 hours). Mean ± SEM calculated rate of transdermal delivery of fentanyl was 8.48 ± 1.7 mg/h (< 36% of the theoretical 25 mg/h). Median steadystate concentration of fentanyl 12 to 100 hours after application of the transdermal patch was 1.58 ng/ml. Plasma concentrations of fentanyl < 1.0 ng/ml were detected in 4 of 6 cats 12 hours after patch application, 5 of 6 cats 18 and 24 hours after application, and 6 of 6 cats 36 hours after application.Conclusions and Clinical Relevance—In cats, transdermal administration provides sustained plasma concentrations of fentanyl citrate throughout a 5- day period. Variation of plasma drug concentrations with transdermal absorption for each cat was pronounced. Transdermal administration of fentanyl has potential for use in cats for long-term control of pain after surgery or chronic pain associated with cancer. (Am J Vet Res2000;61:672–677)}, number={6}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Lee, DD and Papich, MG and Hardie, EM}, year={2000}, month={Jun}, pages={672–677} }
 @article{riddle_lemons_papich_altier_2000, title={Evaluation of ciprofloxacin as a representative of veterinary fluoroquinolones in susceptibility testing}, volume={38}, number={4}, journal={Journal of Clinical Microbiology}, author={Riddle, C. and Lemons, C. L. and Papich, M. G. and Altier, C.}, year={2000}, pages={1636–1637} }
 @article{bermingham_papich_vivrette_2000, title={Pharmacokinetics of enrofloxacin administered intravenously and orally to foals}, volume={61}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.2000.61.706}, abstractNote={AbstractObjective—To determine the pharmacokinetics of enrofloxacin administered IV and orally to foals.Animals—5 clinically normal foals.Procedure—A 2-dose cross-over trial with IV and oral administration was performed. Enrofloxacin was administered once IV (5 mg/kg of body weight) to 1-week-old foals, followed by 1 oral administration (10 mg/kg) after a 7-day washout period. Blood samples were collected for 48 hours after the single dose IV and oral administrations and analyzed for plasma enrofloxacin and ciprofloxacin concentrations by use of high-performance liquid chromatography.Results—For IV administration, mean ± SD total area under the curve (AUC0-∞) was 48.54 ± 10.46 µg · h/ml, clearance was 103.72 ± 0.06 ml/kg/h, halflife (t1/2β) was 17.10 ± 0.09 hours, and apparent volume of distribution was 2.49 ± 0.43 L/kg. For oral administration, AUC0-∞was 58.47 ± 16.37 µg · h/ml, t1/2βwas 18.39 ± 0.06 hours, maximum concentration (Cmax) was 2.12 ± 00.51 µg/ml, time to Cmaxwas 2.20 ± 2.17 hours, mean absorption time was 2.09 ± 0.51 hours, and bioavailability was 42 ± 0.42%.Conclusions and Clinical Relevance—Compared with adult horses given 5 mg of enrofloxacin/kg IV, foals have higher AUC0-∞, longer t1/2β, and lower clearance. Concentration of ciprofloxacin was negligible. Using a target Cmaxto minimum inhibitory concentration ratio of 1:8 to 1:10, computer modeling suggests that 2.5 to 10 mg of enrofloxacin/kg administered every 24 hours would be effective in foals, depending on minimum inhibitory concentration of the pathogen. (Am J Vet Res2000;61: 706–709)}, number={6}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Bermingham, EC and Papich, MG and Vivrette, SL}, year={2000}, month={Jun}, pages={706–709} }
 @article{santschi_papich_2000, title={Pharmacokinetics of gentamicin in mares in late pregnancy and early lactation}, volume={23}, ISSN={["0140-7783"]}, DOI={10.1046/j.1365-2885.2000.00298.x}, abstractNote={The disposition of drugs may differ between pregnant and nonpregnant animals, necessitating a change in dosage. We hypothesized that volume of distribution or clearance may be different for aminoglycoside antibiotics in pregnant mares vs. nonpregnant lactating mares. To examine this hypothesis, we administered gentamicin sulfate to seven Thoroughbred and Quarterhorse mares on two occasions, followed by plasma drug gentamicin assay and pharmacokinetic analysis. The first dose was administered 1–4 weeks before parturition (mean weight 578 kg) and the second dose was administered in the period 1–4 weeks after parturition (mean weight 518 kg). The dose administered at each time was approximately 6.6 mg/kg, intravenously (i.v.). Plasma gentamicin concentrations were determined using fluorescence polarization immunoassay and pharmacokinetic analysis was performed using a two‐compartment open model. The plasma concentration vs. time profiles and total area‐under‐the‐curve were almost identical for mares at late gestation vs. early lactation. Mean volume of distribution at steady‐state was 0.15 (±0.02) and 0.16 (±0.03) L/kg, systemic clearance was 1.06 (±0.17) and 1.11 (±0.17) mL/kg/min, and mean (harmonic) elimination half‐life was 2.2 and 2.1 h, for pregnant and nonpregnant mares, respectively. We concluded that there were no differences in drug distribution and clearance between pregnant and nonpregnant lactating mares. Gentamicin was also assayed in plasma of newborn foals after an injection of 6.6 mg/kg to three of the mares within 60 min of parturition. Gentamicin was undetectable in plasma samples from these foals and, therefore, apparently does not cross the placenta of mares at term.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Santschi, EM and Papich, MG}, year={2000}, month={Dec}, pages={359–363} }
 @article{papich_2000, title={Pharmacologic Considerations for Opiate Analgesic and Nonsteroidal Anti-Inflammatory Drugs}, volume={30}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/s0195-5616(08)70009-3}, DOI={10.1016/s0195-5616(08)70009-3}, abstractNote={When administering opioid analgesic drugs or nonsteroidal anti-inflammatory drugs, veterinarians are often not familiar enough with the underlying pharmacology of the drugs, particularly with the potential for drug interactions and adverse effects. This article considers some of the pharmacologic features of these drugs and provides a basis for important interactions, contraindications, and adverse effects.}, number={4}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Papich, Mark G.}, year={2000}, month={Jul}, pages={815–837} }
 @misc{papich_2000, title={Pharmacologic considerations for opiate analgesic and nonsteroidal anti-inflammatory drugs}, volume={30}, number={4}, journal={Veterinary Clinics of North America. Small Animal Practice}, author={Papich, M. G.}, year={2000}, pages={815} }
 @article{powers_flammer_papich_2000, title={Preliminary investigation of doxycycline plasma concentrations in cockatiels (Nymphicus hollandicus) after administration by injection or in water or feed}, volume={14}, number={1}, journal={Journal of Avian Medicine and Surgery}, author={Powers, L. V. and Flammer, K. and Papich, M.}, year={2000}, pages={23–30} }
 @article{bush_stoskopf_raath_papich_2000, title={Serum oxytetracycline concentrations in African elephant (Loxodonta africana) calves after long-acting formulation injection}, volume={31}, number={1}, journal={Journal of Zoo and Wildlife Medicine}, author={Bush, M. and Stoskopf, M. K. and Raath, J. P. and Papich, M. G.}, year={2000}, pages={41–46} }
 @inbook{bonagura_papich_2000, place={Philadelphia}, edition={13th}, title={Table of Common Drugs: Approximate Dosages}, booktitle={Kirk's Current Veterinary Therapy}, publisher={W.B. Saunders Company}, year={2000}, pages={1241–1264} }
 @article{de jaham_paradis_papich_2000, title={Traditional antifungal dermatologic agents}, volume={22}, number={5}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={De Jaham, C. and Paradis, M. and Papich, M. G.}, year={2000}, pages={461} }
 @article{gookin_riviere_gilger_papich_1999, title={Acute renal failure in four cats treated with paromomycin}, volume={215}, number={12}, journal={Journal of the American Veterinary Medical Association}, author={Gookin, J. L. and Riviere, J. E. and Gilger, B. C. and Papich, M. G.}, year={1999}, pages={1821–1823} }
 @article{olby_sharp_muñana_papich_1999, title={Chronic and Acute Compressive Spinal Cord Lesions in Dogs due to Intervertebral Disc Herniation Are Associated With Elevation in Lumbar Cerebrospinal Fluid Glutamate Concentration}, volume={16}, ISSN={0897-7151 1557-9042}, url={http://dx.doi.org/10.1089/neu.1999.16.1215}, DOI={10.1089/neu.1999.16.1215}, abstractNote={Acute injury to the central nervous system initiates a series of biochemical events that cause secondary tissue damage. The accumulation of excessive concentrations of glutamate in the extracellular space causes excitotoxic damage, and is incriminated as a mediator of this secondary tissue damage. The aim of this study was to measure the concentration of glutamate in cerebrospinal fluid (CSF) obtained from the cerebellomedullary cistern and lumbar subarachnoid space in dogs with acute and chronic compressive injuries of the cervical and thoracolumbar spinal cord, and to correlate the glutamate concentration with injury severity. The results demonstrate that focal injuries of the spinal cord do not affect the glutamate concentration in CSF taken from the cerebellomedullary cistern. However, dogs with severe, acute thoracolumbar disc herniations have two- to 10-fold increases in glutamate concentration in their lumbar CSF at intervals of >12 h after injury. Moreover, the severity of their clinical signs is directly related to the glutamate concentration. Dogs with chronic compressive thoracolumbar lesions have a two-fold elevation of CSF glutamate concentration, suggesting that excitotoxicity may also be a component of chronic spinal cord compression.}, number={12}, journal={Journal of Neurotrauma}, publisher={Mary Ann Liebert Inc}, author={Olby, Natasha J. and Sharp, Nick J.H. and Muñana, Karen R. and Papich, Mark G.}, year={1999}, month={Dec}, pages={1215–1224} }
 @article{tudor_papich_redding_1999, title={Drug disposition and dosage determination of once daily administration of gentamicin sulfate in horses after abdominal surgery}, volume={215}, number={4}, journal={Journal of the American Veterinary Medical Association}, author={Tudor, R. A. and Papich, M. G. and Redding, W. R.}, year={1999}, pages={503–506} }
 @article{breitschwerdt_papich_hegarty_gilger_hancock_davidson_1999, title={Efficacy of Doxycycline, Azithromycin, or Trovafloxacin for Treatment of Experimental Rocky Mountain Spotted Fever in Dogs}, volume={43}, ISSN={0066-4804 1098-6596}, url={http://dx.doi.org/10.1128/AAC.43.4.813}, DOI={10.1128/aac.43.4.813}, abstractNote={ABSTRACT
          
            Dogs were experimentally inoculated with
            Rickettsia rickettsii
            (canine origin) in order to compare the efficacies of azithromycin and trovafloxacin to that of the current antibiotic standard, doxycycline, for the treatment of Rocky Mountain spotted fever. Clinicopathologic parameters, isolation of rickettsiae in tissue culture, and PCR amplification of rickettsial DNA were used to evaluate the response to therapy or duration of illness (untreated infection control group) in the four groups. Concentrations of the three antibiotics in plasma and blood cells were measured by high-performance liquid chromatography. Doxycycline and trovafloxacin treatments resulted in more-rapid defervescence, whereas all three antibiotics caused rapid improvement in attitudinal scores, blood platelet numbers, and the albumin/total-protein ratio. Based upon detection of retinal vascular lesions by fluorescein angiography, trovafloxacin and doxycycline substantially decreased rickettsia-induced vascular injury to the eye, whereas the number of ocular lesions in the azithromycin group did not differ from that in the infection control group. As assessed by tissue culture isolation, doxycycline resulted in the earliest apparent clearance of viable circulating rickettsiae; however, rickettsial DNA could still be detected in the blood of some dogs from all four groups on day 21 postinfection, despite our inability to isolate viable rickettsiae at that point. As administered in this study, trovafloxacin was as efficacious as doxycycline but azithromycin proved less efficacious, possibly due to the short duration of administration.
          }, number={4}, journal={Antimicrobial Agents and Chemotherapy}, publisher={American Society for Microbiology}, author={Breitschwerdt, E. B. and Papich, M. G. and Hegarty, B. C. and Gilger, B. and Hancock, S. I. and Davidson, M. G.}, year={1999}, month={Apr}, pages={813–821} }
 @article{stamper_papich_lewbart_may_plummer_stoskopf_1999, title={Pharmacokinetics of ceftazidime in loggerhead sea turtles (Caretta caretta) after single intravenous and intramuscular injections}, volume={30}, number={1}, journal={Journal of Zoo and Wildlife Medicine}, author={Stamper, M. A. and Papich, M. G. and Lewbart, G. A. and May, S. B. and Plummer, D. D. and Stoskopf, M. K.}, year={1999}, pages={32–35} }
 @article{papich_1999, title={Pharmacokinetics of enrofloxacin in reptiles}, volume={21}, number={12M}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Papich, M.G.}, year={1999}, pages={110–114} }
 @article{breuhaus_degraves_honore_papich_1999, title={Pharmacokinetics of ibuprofen after intravenous and oral administration and assessment of safety of administration to healthy foals}, volume={60}, number={9}, journal={American Journal of Veterinary Research}, author={Breuhaus, B. A. and Degraves, F. J. and Honore, E. K. and Papich, M. G.}, year={1999}, pages={1066–1073} }
 @article{murphey_santschi_papich_1999, title={Regional intravenous perfusion of the distal limb of horses with amikacin sulfate}, volume={22}, ISSN={["0140-7783"]}, DOI={10.1046/j.1365-2885.1999.00180.x}, abstractNote={Journal of Veterinary Pharmacology and TherapeuticsVolume 22, Issue 1 p. 68-71 Regional intravenous perfusion of the distal limb of horses with amikacin sulfate Murphey, Murphey Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47906, USA. Present address: Department of Surgery, Shriners Burns Institute, University of Texas Medical Branch, Galveston, TX, 77555–0833, USA,Search for more papers by this author Santschi, Santschi Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47906, USA. Present address: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA,Search for more papers by this author Papich, Papich Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh North Carolina 27606, USASearch for more papers by this author Murphey, Murphey Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47906, USA. Present address: Department of Surgery, Shriners Burns Institute, University of Texas Medical Branch, Galveston, TX, 77555–0833, USA,Search for more papers by this author Santschi, Santschi Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47906, USA. Present address: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, Wisconsin 53706, USA,Search for more papers by this author Papich, Papich Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh North Carolina 27606, USASearch for more papers by this author First published: 05 January 2002 https://doi.org/10.1046/j.1365-2885.1999.00180.xCitations: 82 Papich Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh North Carolina 27606, USA Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume22, Issue1January 1999Pages 68-71 RelatedInformation}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Murphey, ED and Santschi, EM and Papich, MG}, year={1999}, month={Feb}, pages={68–71} }
 @misc{ihrke_papich_demanuelle_1999, title={The use of fluoroquinolones in veterinary dermatology}, volume={10}, ISSN={["0959-4493"]}, DOI={10.1046/j.1365-3164.1999.00179.x}, abstractNote={The fluoroquinolones are a group of antibiotics with considerable application for use in veterinary dermatology. They are rapidly bactericidal against a wide variety of clinically important organisms includingStaphylococcus intermediusand gram‐negative enteric bacilli by virtue of interference with the supercoiling of bacterial chromosomal material. Their favourable pharmacokinetic features make them applicable in many animal species, and in a range of dose formulations. The only major clinical contraindication is that fluoroquinolones should not be given to young, rapidly growing dogs as they can induce a noninflammatory, erosive arthropathy. For many years the only veterinary‐labelled fluoroquinolone available was enrofloxacin. The selection of a fluoroquinolone has become more complex now that there are more choices available. Orbifloxacin, difloxacin and marbofloxacin now join enrofloxacin on the veterinary market, although not all of these are licensed in every country. The use of fluoroquinolones in dermatology remains controversial. The authors recommend that fluoroquinolones be considered in circumstances where canine pyoderma has been refractory to appropriate ‘first line’ antibiotics. They are most useful in the management of recurrent pyoderma and in chronic, deep pyoderma with extensive scar tissue. In addition, fluouroquinolones frequently are the drugs of choice for canine ear infections caused byPseudomonas aeruginosa.}, number={3}, journal={VETERINARY DERMATOLOGY}, author={Ihrke, PJ and Papich, MG and Demanuelle, TC}, year={1999}, month={Sep}, pages={193–204} }
 @article{papich_1998, title={Antibacterial choices for skin infections}, volume={12}, number={1998}, journal={North American Veterinary Conference. Veterinary Proceedings}, author={Papich, M. G.}, year={1998}, pages={188–190} }
 @article{papich_1998, title={Antibacterial drug therapy - Focus on new drugs}, volume={28}, ISSN={["0195-5616"]}, DOI={10.1016/S0195-5616(98)82002-0}, abstractNote={This article will focus on the drugs for which there has been a recent or renewed interest in veterinary medicine. Some of these are new drugs that were recently introduced. Others discussed may be human-label drugs for which there has been recent interest in veterinary medicine because of the need for a more active drug or convenient regimen. For drugs such as the aminoglycosides included here, recent information has provided us with updated dosage guidelines.}, number={2}, journal={VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE}, author={Papich, MG}, year={1998}, month={Mar}, pages={215-+} }
 @article{kyles_hardie_hansen_papich_1998, title={Comparison of transdermal fentanyl and intramuscular oxymorphone on post-operative behaviour after ovariohysterectomy in dogs}, volume={65}, ISSN={["0034-5288"]}, DOI={10.1016/S0034-5288(98)90151-5}, abstractNote={The effects of transdermal fentanyl and i.m. oxymorphone on behavioural and physiological responses, after ovariohysterectomy in dogs, were investigated. The study involved three groups of 10 dogs: fentanyl/surgery (FS), oxymorphone/surgery (OS), fentanyl/control (FC). A transdermal fentanyl delivery system (50 microg hour(-1)) (FS and FC) was applied 20 hours before surgery, or i.m. oxymorphone (OS) was administered. After ovariohysterectomy (FS and OS) or anaesthesia alone (FC), dogs were continuously videotaped for 24 hours and a standardised hourly interaction with a handler performed. The videotapes were analysed, and interactive and non-interactive behaviours evaluated. In addition, pain and sedation scores, pulse and respiratory rates, rectal temperature, arterial blood pressure, plasma cortisol and plasma fentanyl concentrations were measured. This study showed that transdermal fentanyl and i.m. oxymorphone (0.05 mg kg(-1)) produced comparable analgesic effects over a 24 hour recording period. I.m. oxymorphone produced significantly more sedation and lower rectal temperatures than transdermal fentanyl. There were no significant differences between groups in respiratory and heart rates, and arterial blood pressures.}, number={3}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Kyles, AE and Hardie, EM and Hansen, BD and Papich, MG}, year={1998}, pages={245–251} }
 @article{korsrud_salisbury_rhodes_papich_yates_bulmer_macneil_landry_lambert_yong_et al._1998, title={Depletion of penicillin G residues in tissues, plasma and injection sites of market pigs injected intramuscularly with procaine penicillin G}, volume={15}, ISSN={0265-203X}, url={http://dx.doi.org/10.1080/02652039809374662}, DOI={10.1080/02652039809374662}, abstractNote={Procaine penicillin G was administered by intramuscular (i.m.) injection to groups of healthy 100 kg market pigs at the approved label dose (15,000 IU/kg body weight), once daily for three consecutive days; or an extra-label dose (66,000 IU/kg body weight), once daily for five consecutive days. Penicillin G residue depletion was followed in plasma, tissue and injection sites using a liquid chromatographic method. Groups of pigs were killed 1, 2, 3, 4, 5 and 8 days after the last injection with the label dose. Penicillin G was not detected in liver after 1 day of withdrawal, in muscle and fat after 2 days of withdrawal, in plasma after 4 days of withdrawal, in skin after 5 days of withdrawal, or in kidney and the injection sites after 8 days of withdrawal. Other groups of pigs were killed 1, 2, 3, 5 and 7 days after injection with the extra-label dose. In these pigs penicillin G was not found in liver after 2 days of withdrawal, in fat after 3 days of withdrawal, or in the muscle, skin, plasma and injection sites after 7 days of withdrawal. Penicillin G was found at all times in the kidneys of the groups of pigs that received the high dose. The technique used for neck injections was critical to obtain intramuscular rather than intermuscular injections. The Bureau of Veterinary Drugs, Health Protection Branch, Health Canada calculated that the appropriate withdrawal period for pigs was 8 days for a dose of 15,000 IU procaine penicillin G/kg body weight and 15 days for a dose of 66,000 IU/kg.}, number={4}, journal={Food Additives and Contaminants}, publisher={Informa UK Limited}, author={Korsrud, G. O. and Salisbury, C. D. C. and Rhodes, C. S. and Papich, M. G. and Yates, W. D. G. and Bulmer, W. S. and MacNeil, J. D. and Landry, D. A. and Lambert, G. and Yong, M. S. and et al.}, year={1998}, month={May}, pages={421–426} }
 @article{mcfarlane_sellon_gaffney_hedgpeth_papich_gibbs_1998, title={Hematologic and serum biochemical variables and plasma corticotropin concentration in healthy aged horses}, volume={59}, number={10}, journal={American Journal of Veterinary Research}, author={McFarlane, D. and Sellon, D. C. and Gaffney, D. and Hedgpeth, V. and Papich, M. and Gibbs, S.}, year={1998}, pages={1247–1251} }
 @article{papich_1998, title={Optimum strategy for antibacterial therapy}, volume={12}, number={1998}, journal={North American Veterinary Conference. Veterinary Proceedings}, author={Papich, M. G.}, year={1998}, pages={607–608} }
 @article{cook_papich_roberts_bowman_1998, title={Pharmacokinetics of cisapride in horses after intravenous and rectal administration: Erratum}, volume={59}, number={4}, journal={American Journal of Veterinary Research}, author={Cook, G. and Papich, M. G. and Roberts, M. C. and Bowman, K. F.}, year={1998}, pages={396} }
 @article{martin-jimenez_papich_riviere_1998, title={Population pharmacokinetics of gentamicin in horses}, volume={59}, number={12}, journal={American Journal of Veterinary Research}, author={Martin-Jimenez, T. and Papich, M. G. and Riviere, J. E.}, year={1998}, pages={1589–1598} }
 @article{young_schumacher_papich_jacobson_1997, title={Disposition of enrofloxacin and its metabolite ciprofloxacin after intravascular injection in juvenile burmese pythons (Python molurus bivittatus)}, volume={28}, number={1}, journal={Journal of Zoo and Wildlife Medicine}, author={Young, L. A. and Schumacher, J. and Papich, M. G. and Jacobson, E. R.}, year={1997}, pages={71–79} }
 @article{kordick_papich_breitschwerdt_1997, title={Efficacy of enrofloxacin or doxycycline for treatment of Bartonella henselae or Bartonella clarridgeiae infection in cats.}, volume={41}, ISSN={0066-4804 1098-6596}, url={http://dx.doi.org/10.1128/AAC.41.11.2448}, DOI={10.1128/aac.41.11.2448}, abstractNote={Enrofloxacin and doxycycline are antimicrobial agents used to treat bacterial diseases of cats. In vitro susceptibility data indicate that either drug should be effective against Bartonella species. In vivo efficacies of these drugs for eradication of chronic Bartonella henselae or Bartonella clarridgeiae infections were examined in 18 experimentally infected cats and 25 naturally exposed cats treated with enrofloxacin (22.7 mg given orally [PO] every 12 h [q12h] [14 days, n = 10; 28 days, n = 13]) or with doxycycline (25 mg PO q12h [14 days, n = 9; 28 days, n = 8]) or not treated (n = 3). Plasma drug concentrations were determined in experimental cats by high-performance liquid chromatography. Only 23 of 43 cats enrolled ultimately met inclusion criteria. Bacteremia was eliminated for 12 to 25 weeks posttreatment in four of seven cats receiving 14 days of enrofloxacin, five of seven cats receiving 28 days of enrofloxacin, one of six cats receiving 14 days of doxycycline, and one of two cats receiving 28 days of doxycycline. Defining a negative result by blood culture as treatment success may be erroneous; these results may reflect the insensitivity of blood culture or the relapsing nature of Bartonella bacteremia. Our results suggest that MICs obtained with axenic media do not predict antimicrobial activity against intracellular Bartonella, that a long treatment course is required to eliminate infection, and that duration of therapy correlates with pretreatment bacterial load. Given current concern about the development of antimicrobial resistance, we would reserve recommendation for treatment to cats owned by an immunocompromised individual or as an alternative to euthanasia of a pet.}, number={11}, journal={Antimicrobial Agents and Chemotherapy}, publisher={American Society for Microbiology}, author={Kordick, D L and Papich, M G and Breitschwerdt, E B}, year={1997}, month={Nov}, pages={2448–2455} }
 @inbook{papich_1997, place={Baltimore}, title={Formulary}, booktitle={The 5 Minute Veterinary Consult}, publisher={Williams & Wilkins}, author={Papich, M.G.}, editor={Tilley, L.P. and Smith, F.W.K.Editors}, year={1997}, pages={1180–1240} }
 @article{cook_papich_roberts_bowman_1997, title={Pharmacokinetics of cisapride in horses after intravenous and rectal administration}, volume={58}, number={12}, journal={American Journal of Veterinary Research}, author={Cook, G. and Papich, M. G. and Roberts, M. C. and Bowman, K. F.}, year={1997}, pages={1427–1430} }
 @article{page_papich_1997, title={Pharmacology and toxicology special issue}, volume={28}, number={1}, journal={Journal of Zoo and Wildlife Medicine}, author={Page, C. D. and Papich, M. G.}, year={1997}, pages={1–2} }
 @article{breitschwerdt_davidson_hegarty_papich_grindem_1997, title={Prednisolone at anti-inflammatory or immunosuppressive dosages in conjunction with doxycycline does not potentiate the severity of Rickettsia rickettsii infection in dogs.}, volume={41}, ISSN={0066-4804 1098-6596}, url={http://dx.doi.org/10.1128/AAC.41.1.141}, DOI={10.1128/aac.41.1.141}, abstractNote={Dogs were experimentally inoculated with Rickettsia rickettsii to determine if anti-inflammatory or immunosuppressive dosages of prednisolone, when administered in conjunction with an antirickettsial antibiotic (doxycycline), induced therapeutically relevant pathophysiological consequences that ultimately influence disease outcome. Although the duration of rickettsemia was prolonged in dogs receiving immunosuppressive, but not anti-inflammatory, corticosteroids, concurrent administration of doxycycline and corticosteroids conferred no other detected detrimental effects. Treatment with doxycycline or doxycycline in conjunction with prednisolone resulted in decreased R. rickettsii-specific antibody titers; however, examination of appropriately timed acute- and convalescent-phase serum samples would have facilitated an accurate diagnosis of Rocky Mountain spotted fever (RMSF) in all 16 dogs. We conclude that the concurrent use of anti-inflammatory or immunosuppressive doses of prednisolone in conjunction with doxycycline, early in the course of experimental RMSF, confers no clinically relevant detrimental effects and that additional studies might be indicated to detect possible beneficial effects in cases of severe or potentially fulminant RMSF. However, because the illness induced in these dogs was of mild to moderate severity, the results of this study should definitely not be construed as supporting the safety or efficacy of prednisolone for treatment of severe canine or human RMSF.}, number={1}, journal={Antimicrobial Agents and Chemotherapy}, publisher={American Society for Microbiology}, author={Breitschwerdt, E B and Davidson, M G and Hegarty, B C and Papich, M G and Grindem, C B}, year={1997}, month={Jan}, pages={141–147} }
 @misc{papich_1997, title={Principles of analgesic drug therapy}, volume={12}, ISSN={["0882-0511"]}, DOI={10.1016/S1096-2867(97)80005-9}, abstractNote={The drugs most often used for pain relief in animals are the nonsteroidal antiinflammatory drugs (NSAIDS) and the opioid analgesics. The NSAIDS are effective, inexpensive, and long-acting drugs, but their degree of analgesia is limited by the adverse effects at high doses. The most common adverse effect from NSAIDS is gastritis and gastrointestinal hemorrhage and ulceration. This is most common from high doses, or from using NSAIDS not appropriate for dogs such as ibuprofen or indomethacin. The NSAIDS used in dogs include aspirin, phenylbutazone, naproxen, piroxicam, ketoprofen, and carprofen. Carprofen is a new drug with a low incidence of side effects and its popularity is increasing at a fast rate. For more acute pain, especially acute pain from surgery or trauma, opioids are frequently administered. Opioids have the advantage of higher efficacy when the dose is increased. The incidence of adverse effects is low, but side effects of sedation are common. An important disadvantage of opioids is their short duration and low oral absorption, which necessitates a frequent injection or i.v. infusion for most patients. Recent studies have established other applications for administration of opioids such as a transdermal fentanyl patch. These applications offer new possibilities for convenient administration.}, number={2}, journal={SEMINARS IN VETERINARY MEDICINE AND SURGERY-SMALL ANIMAL}, author={Papich, MG}, year={1997}, month={May}, pages={80–93} }
 @article{anderson_moats_rushing_wesen_papich_1996, title={Ampicillin and amoxicillin residue detection in milk, using microbial receptor assay (Charm II) and liquid chromatography methods, after extra-label administration of the drugs to lactating cows}, volume={57}, journal={American Journal of Veterinary Research}, author={Anderson, K.L. and Moats, W.A. and Rushing, J.E. and Wesen, D.P. and Papich, M.G.}, year={1996}, pages={73–78} }
 @article{kyles_papich_hardie_1996, title={Disposition of transdermally administered fentanyl in dogs}, volume={57}, journal={American Journal of Veterinary Research}, author={Kyles, A.E. and Papich, M.G. and Hardie, E.M.}, year={1996}, pages={715–719} }
 @article{papich_1996, title={Drug Residue Considerations for Anesthetics and Adjunctive Drugs in Food-Producing Animals}, volume={12}, ISSN={0749-0720}, url={http://dx.doi.org/10.1016/s0749-0720(15)30393-5}, DOI={10.1016/s0749-0720(15)30393-5}, abstractNote={This article is a summary of residue concerns for anesthetics and anesthetic adjuncts used in food animals. The risks associated with residues of these drugs in food-producing animals, as well as the veterinarian's responsibility to reduce this risk, are discussed. The potential for residues and suggestions for prevention in each of the major anesthetic drug classes are described. Suggested withdrawal times are proposed for nonapproved drugs used off label. Each class of drug is summarized in the tables.}, number={3}, journal={Veterinary Clinics of North America: Food Animal Practice}, publisher={Elsevier BV}, author={Papich, Mark G.}, year={1996}, month={Nov}, pages={693–706} }
 @article{korsrud_papich_fesser_salisbury_macneil_1996, title={Laboratory Testing of the Charm Test II Receptor Assays and the Charm Farm Test with Tissues and Fluids from Hogs Fed Sulfamethazine, Chlortetracycline, and Penicillin G}, volume={59}, ISSN={0362-028X}, url={http://dx.doi.org/10.4315/0362-028x-59.2.161}, DOI={10.4315/0362-028x-59.2.161}, abstractNote={The potentials of the Charm Test II receptor assays for the detection of residues of sulfonamides, tetracyclines, and β-lactams and the Charm Farm Test for screening for antimicrobial residues were tested. Market hogs were fed rations containing three times the label level of sulfamethazine, chlortetracycline, and penicillin G for 2 weeks. Groups were killed after 0, 2, 4 and 8 days of withdrawal. Quantitative chemical methods were used to determine residue levels in fluids and tissues. Results were compared with those obtained using the qualitative Charm Test II receptor assays and the Charm Farm Test antimicrobial inhibition assay. For the Charm Test II assays for sulfonamides, tetracyclines and β-lactams, respectively, 1.6, 5, and 6% of the results were false positive and 7, 5, and 0% were false negative, based on the limits of detection for the test kits and the quantitative results. On a similar basis for the Charm Farm Test, 16% of the results were false positive (6 kidney, 4 muscle, and 6 urine samples) and 1% were false negative (sulfamethazine in one urine sample).}, number={2}, journal={Journal of Food Protection}, publisher={International Association for Food Protection}, author={Korsrud, Gary O. and Papich, Mark G. and Fesser, Adrian C. E. and Salisbury, Craig D. C. and Macneil, James D.}, year={1996}, month={Feb}, pages={161–166} }
 @article{marcellin-little_papich_richardson_deyoung_1996, title={Pharmacokinetic model for cefazolin distribution during total hip arthroplasty}, volume={57}, journal={American Journal of Veterinary Research}, author={Marcellin-Little, D.J. and Papich, M.G. and Richardson, D.C. and DeYoung, D.J.}, year={1996}, pages={720–723} }
 @article{korsrud_papich_fesser_salisbury_macneil_1996, title={Residue depletion in tissues and fluids from swine fed sulfamethazine, chlortetracycline and penicillin G in combination}, volume={13}, ISSN={0265-203X}, url={http://dx.doi.org/10.1080/02652039609374410}, DOI={10.1080/02652039609374410}, abstractNote={Twenty-four hogs were fed a ration for 14 days containing three times the recommended label dose of a combination drug which included sulfamethazine, chlortetracycline and penicillin G. Groups of six hogs were slaughtered 0, 2, 4, or 8 days after withdrawal. Six untreated control hogs were slaughtered 5 days before the first group, of six treated hogs, were slaughtered. Residue concentrations were determined in kidney, liver, muscle, serum and urine. At zero withdrawal the kidney from one hog contained 0.018 mg penicillin G per kg and the serum from the same hog contained 0.016 mg penicillin G per litre. Penicillin G was not detected in any other samples that were analysed. Chlortetracycline concentrations in tissues at zero withdrawal time were below accepted Canadian Maximum Residue Limits (MRL) for chlortetracycline of 1 mg/kg in muscle, 2 mg/kg in liver and 4 mg/kg in kidney and were below the limit of quantitation in all tissues 4 days after withdrawal. Sulfamethazine persisted in the tissues longer than penicillin G or chlortetracycline. Sulfamethazine concentrations were above the Canadian MRL of 0.1 mg/kg at zero withdrawal time and did not decrease to below the MRL until 8 days after withdrawal. Our results suggest that, if the label withdrawal period of 10 days is observed, an increase in the dosage of up to three times the recommended rate is unlikely to increase significantly the risk that residues would occur in the tissues of treated hogs at concentrations which exceed MRLs. Sulfamethazine concentrations in all matrices decreased after storage at -76 degrees C for 6 months.}, number={3}, journal={Food Additives and Contaminants}, publisher={Informa UK Limited}, author={Korsrud, G. O. and Papich, M. G. and Fesser, A. C. E. and Salisbury, C. D. C. and Macneil, J. D.}, year={1996}, month={Apr}, pages={287–292} }
 @article{papich_alcorn_1995, title={Absorption of diazepam after its rectal administration in dogs}, volume={56}, number={12}, journal={American Journal of Veterinary Research}, author={Papich, M. G. and Alcorn, J.}, year={1995}, pages={1629} }
 @article{papich_1995, title={An American Veterinary Medical Association perspective [Professional flexible labeling. An interactive workshop on first principles, April, 1995]}, volume={207}, number={7}, journal={Journal of the American Veterinary Medical Association}, author={Papich, M. G.}, year={1995}, pages={871} }
 @inbook{papich_1995, place={Philadelphia}, edition={4th}, title={Antimicrobial drugs}, booktitle={Textbook of Veterinary Internal Medicine}, publisher={W.B. Saunders Company}, author={Papich, M.G.}, editor={Ettinger, S.J. and Feldman, E.CEditors}, year={1995}, pages={272–283} }
 @article{boison_korsrud_papich_macneil_1995, title={Comparison of four commercially available rapid test kits with liquid chromatography for detecting penicillin G residues in bovine plasma}, volume={78}, journal={Journal of AOAC International}, author={Boison, J.O. and Korsrud, G.O. and Papich, M.G. and MacNeil, J.D.}, year={1995}, pages={1144–1152} }
 @inbook{vaden_papich_1995, place={Philadelphia}, edition={12th}, title={Empiric antibiotic therapy}, booktitle={Kirk's Current Veterinary Therapy}, publisher={W.B. Saunders Company}, author={Vaden, S.L. and Papich, M.G.}, editor={Bonagura, J.D.Editor}, year={1995}, pages={276–279} }
 @inbook{papich_1995, place={Philadelphia}, edition={12th}, title={Incompatible critical care drug combinations}, booktitle={Kirk's Current Veterinary Therapy}, publisher={W.B. Saunders Company}, author={Papich, M.G.}, editor={Bonagura, J.D.Editor}, year={1995}, pages={194–198} }
 @book{bonagura_warren_papich_1995, place={Philadelphia}, edition={12th}, title={Kirk's Current Veterinary Therapy}, publisher={W.B. Saunders Company}, year={1995} }
 @article{papich_wright_petrie_korsrud_1995, title={PHARMACOKINETICS OF OXYTETRACYCLINE ADMINISTERED INTRAVENOUSLY TO 4 TO 5 DAY-OLD FOALS}, volume={18}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.1995.tb00607.x}, abstractNote={Journal of Veterinary Pharmacology and TherapeuticsVolume 18, Issue 5 p. 375-378 Pharmacokinetics of oxytetracycline administered intravenously to 4 to 5 - day-old foals M.G. PAPICH, M.G. PAPICH *Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606Search for more papers by this authorA.K. WRIGHT, A.K. WRIGHT †Department of Veterinary Internal Medicine, Western College of Veterinary Medicine, Saskatoon, Canada S7N 5B4 Equine Medical Associates, 17525 Manchester Road, Glencoe, Missouri 63038, USASearch for more papers by this authorL. PETRIE, L. PETRIE †Department of Veterinary Internal Medicine, Western College of Veterinary Medicine, Saskatoon, Canada S7N 5B4Search for more papers by this authorG.O. KORSRUD, G.O. KORSRUD ‡Health of Animals laboratory, Agriculture Canada, 116 Veterinary Road, Saskatoon. Canada S7N 5E3Search for more papers by this author M.G. PAPICH, M.G. PAPICH *Department of Anatomy, Physiological Sciences, and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606Search for more papers by this authorA.K. WRIGHT, A.K. WRIGHT †Department of Veterinary Internal Medicine, Western College of Veterinary Medicine, Saskatoon, Canada S7N 5B4 Equine Medical Associates, 17525 Manchester Road, Glencoe, Missouri 63038, USASearch for more papers by this authorL. PETRIE, L. PETRIE †Department of Veterinary Internal Medicine, Western College of Veterinary Medicine, Saskatoon, Canada S7N 5B4Search for more papers by this authorG.O. KORSRUD, G.O. KORSRUD ‡Health of Animals laboratory, Agriculture Canada, 116 Veterinary Road, Saskatoon. Canada S7N 5E3Search for more papers by this author First published: October 1995 https://doi.org/10.1111/j.1365-2885.1995.tb00607.xCitations: 10 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat REFERENCES Brewer, B.D., Clement, S.F., Lota, W.S. & Gronwall, R, (1988a) Single injection inulin/PAH method for the determination of renal clearances in adult horses and ponies. Journal of Veterinary Pharmacology and Therapeutics. 11, 409–412. Brewer, B.D., Clement S.F., Lotz, W.S. and Gronwall, R. (1988b) Renal function in neonatal foals and their dams: a comparison of inulin. para-atninohippuric add, and endogenous creatinine clearances. Equine Veterinary Journal, Suppl. 5, 51. Brown, M.P., Gronwell, R., Knoll, W.R. & Beal, C. (1984a) Ampiclilin trihydrate in foals: serum concentrations and clearance after a single oral dose. Equine Veterinary Journal, 16, 371–373. Brown, M.P., Gronwell, R.R., Boos, D. & Beal, C. (1984b) Aqueous procaine penicillin G in foals, serum concentrations and pharmacokinetics after a single intramuscular dose. Equine Veterinary Journal, 16, 374–375. Brown, M.P., Gronwell, R.R., Martinez, D.S. & Beal, C. (1986) Pharmacokinetics of amikacin in pony foals after a single intramuscular injection. American Journal of Veterinary Research, 47, 453–454. Button, C. & Mülders, M.S.G. (1984) Effects of oxytetracycline in propylene glycol, oxytetracydlne in saline solution, and propylene glycol alone on blood ionized calcium and plasma total calcium in sheep. American Journal of Veterinary Research, 45, 1658–1659. Caprile, K.A. & Short, C.R. (1987) Pharmacologic considerations in drug therapy in foals. Veterinary Clinics of Sorth America (Equine Practice), 3, 123–144. Carter, G.K., Martens, R.J., Brown, S.A. & Martin, M.T. (1986) Phannacokinetics of sodium amoxicillin in foals after intramuscular administration. American Journal of Veterinary Research. 47, 2126–2128. Cummings, L.E., Guthrie, A.J., Harkins, J.D. & Short, C.R. (1990) Pbarmacokinetics of gentamicin in newborn to 30-day-old foals. American Journal of Veterinary Research. 51, 1988–1992. Gibaldi, M., Perrier, O. (1982) Pharmacokinetlcs, 2nd Edn Marcel Dekker Inc, New York . Gross, D.R., Kitzman, J.V. & Adams, H.R. (1979) Cardiovascular effects of intravenous administration of propylene glycol and of oxytetracydine in propylene glycol in calves. American Journal of Veterinary Research. 40, 783–791. Gross, D.R., Dodd, K.T., Williams, J.D. & Adams, H.R. (1981) Adverse cardiovascular effects of oxytetracydine preparations and vehicles in Intact awake calves. American Journal of Veterinary Research, 42, 1371–1377. Gyrd-Hansen, N., Rasmussea F. & Smith, M. (1981) Cardiovascular effects of intravenous administration of tetracycline in cattle. Journal of Veterinary Pharmacology and Therapeutics, 4, 15–2 5. Kasper, C.A., Clayton, H.M., Wright, A.K., Skuba, E.V. & Petrie, L. (1995) Effects of high doses of oxytetracydine on metacarpophalangeal joint kinematics in neonatal foals. Journal of the American Veterinary Medical Association. 207, 71–73. Kohn, C.W. & Strasser, S.L. (1986) 24-hour renal dearance and excretion of endogenous substances in the mare. American Journal of Veterinary Research. 47, 1332–1337. Lairmore, M.D., Alexander, A.F., Powers, B.E., Milisen. W.E., McChesney, A.E. & Spraker, T.S. (1984) Qxytetracycline-assodated nephrotoxicosis in feedlot calves. Journal of the American Veterinary Medical Association, 185, 793–795. Lokai, M.D. (1992) Case selection for medical management of congenital flexural deformities in foals. Veterinary Clinics of North America (Equine Practice). 14(4), 23–25. Madison, J.B., Garber, J.L. Rice, B., Stumf, A.J., Zimmer, A.E. & Ott. EA. (1994) Effect of oxytetracydine on metacarpophalangeal and distal Interphalangeal joint angles in newborn foals. Journal of the American Veterinary Medical Association, 204, 246–249. MacNeil, J.D., Korsrud, G.O., Naylor, J.N. & Yates, W.D.G. (1989) Bioassay techniques and high-performance liquid chromatography for detection of oxytetracydine residues in tissues from calves. American Journal of Veterinary Research. 50, 72–74. Prescott, J.F. & Baggot, J.D. (1993) Prindpies of antimicrobial drug disposition. In: Antimicrobial Therapy in Veterinary Medicine. 2nd Edn, pp. 37–60, Iowa State University Press, Ames , Iowa . Riond, J-L. & Riviere, J.E. (1989) Effects of tetracydines on the kidney in cattle and dogs. Journal of the American Veterinary Medical Association, 195, 995–997. Sweeney, R.W., Beech, J. & Simmons, R.D. (1988) Pharmacokinetlcs of intravenously and intramuscularly administered ticarcillin and clavuIanic add in foals. American Journal of Veterinary Research, 48, 23–26. Teske, R.H., Rollins, L.D., Condon, R.J. & Carter, G.G. (1973) Serum oxytetracydine concentrations after intravenous and intramuscular administration in horses. Journal of the American Veterinary Medical Association, 162, 119–120. Vaala, W.E., Ehnen, S.J. & Divers, T.J. (1987) Acute renal failure associated with administration of excessive amounts of tetracycline in a cow. Journal of the American Veterinary Medical Association, 191, 1601–1603. Vivrette, S., Cowgill, L.D., Pascoe, J., Suter, C. & Becker, T. (1993) Hemodialysis for treatment of oxytetracyline-induced acute renal failure in a neonatal foal. Journal of the American Veterinary Medical Association, 203, 105–107. Wright A.K. Petrie, L., Papich, M.G., Archer, J. & Fretz, P.B. (1992) Effect of high-dose oxytetracydine on renal parameters in neonatal foals. Proceedings of the American Association of Equine Practitioners, 38, 297–298. Yamaoka, K., Nakagawa, T. & Uno, T. (1978) Application of Akaike's Information Criterion (AIC) in the evaluation of linear pharmacokinetic equations. Journal of Pharmacokinetlcs and Blopharmaceutics, 6, 165–175. Citing Literature Volume18, Issue5October 1995Pages 375-378 ReferencesRelatedInformation}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={PAPICH, MG and WRIGHT, AK and PETRIE, L and KORSRUD, GO}, year={1995}, month={Oct}, pages={375–378} }
 @inbook{papich_1995, place={Philadelphia}, edition={4th}, title={Pharmacologic principles}, booktitle={Textbook of Veterinary Internal Medicine}, publisher={W.B. Saunders Company}, author={Papich, M.G.}, editor={Ettinger, S.J. and Feldman, E.CEditors}, year={1995}, pages={264–271} }
 @article{anderson_moats_rushing_wesen_papich_1995, title={Potential for oxytetracycline administration by three routes to cause milk residues in lactating cows, as detected by radioimmunoassay (Charm II) and high-performance liquid chromatography test methods}, volume={56}, journal={American Journal of Veterinary Research}, author={Anderson, K.L. and Moats, W.A. and Rushing, J.E. and Wesen, D.P. and Papich, M.G.}, year={1995}, pages={70–77} }
 @article{beck_loomis_lewbart_spelman_papich_1995, title={Preliminary comparison of plasma concentrations of gentamicin injected into the cranial and caudal limb musculature of the eastern box turtle (Terrapene carolina carolina)}, volume={26}, number={2}, journal={Journal of Zoo and Wildlife Medicine}, author={Beck, K. and Loomis, M. and Lewbart, G. and Spelman, L. and Papich, M.}, year={1995}, pages={265–268} }
 @article{papich_1995, title={Professional flexible labeling: an American Veterinary Medical Association perspective}, volume={207}, journal={Journal of the American Veterinary Medical Association}, author={Papich, M.G.}, year={1995}, pages={871–874} }
 @inbook{papich_davidson_1995, place={Philadelphia}, edition={12th}, title={Unapproved use of drugs in animals}, booktitle={Kirk's Current Veterinary Therapy}, publisher={W.B. Saunders Company}, author={Papich, M.G. and Davidson, Gigi}, editor={Bonagura, J.D.Editor}, year={1995}, pages={48–52} }
 @article{korsrud_boison_papich_yates_macneil_janzen_mckinnon_landry_lambert_yong_et al._1994, title={Depletion of penicillin G residues in tissues and injection sites of yearling beef steers dosed with benzathine penicillin G alone or in combination with procaine penicillin G}, volume={11}, ISSN={0265-203X}, url={http://dx.doi.org/10.1080/02652039409374196}, DOI={10.1080/02652039409374196}, abstractNote={The contribution of benzathine penicillin G to residues in tissues and injection sites of yearling beef steers was assessed by treating seven groups of five to seven steers with either benzathine and procaine penicillin G together or benzathine penicillin G alone. Steers were injected with a commercial combination of benzathine and procaine penicillin G according to the Canadian (intramuscular) or United States (subcutaneous) label dosages of 8600 and 8800 IU penicillin G/kg body weight, respectively. They were killed 14 or 30 days after the intramuscular injections, and 30 days after the subcutaneous injections. At the label withdrawal times, Canadian 14 days and United States 30 days, the levels in the injection sites for all of the treatments were 30-60 times above the Canadian and United States' Maximum Residue Limit of 50 micrograms/kg, while liver, kidney and gluteal muscle levels were below the Maximum Residue Limit. Other steers were injected intramuscularly with 24,000 IU benzathine/procaine penicillin G/kg body weight and slaughtered 8, 14 or 50 days after injection. Fifty-day injection site residues were 24 times the Maximum Residue Limit. Another group of steers was injected intramuscularly with benzathine penicillin G alone at 12,000 IU/kg body weight and slaughtered 14 days later. Penicillin G levels in the injection sites were 156 times the Maximum Residue Limit. The persistence of penicillin G residues at the injection sites in all the treatment groups appears to be attributable primarily to benzathine penicillin G. Visual inspection of muscle surfaces did not reliably reveal all injection site lesions in the underlying musculature.}, number={1}, journal={Food Additives and Contaminants}, publisher={Informa UK Limited}, author={Korsrud, G. O. and Boison, J. O. and Papich, M. G. and Yates, W. D. G. and Macneil, J. D. and Janzen, E. D. and Mckinnon, J. J. and Landry, D. A. and Lambert, G. and Yong, M. S. and et al.}, year={1994}, month={Jan}, pages={1–6} }
 @article{papich_korsrud_boison_yates_macneil_janzen_mckinnon_landry_1994, title={Disposition of penicillin G after administration of benzathine penicillin G, or a combination of benzathine penicillin G and procaine penicillin G in cattle}, volume={55}, number={6}, journal={American Journal of Veterinary Research}, author={Papich, M. G. and Korsrud, G. O. and Boison, J. O. and Yates, W. D. G. and MacNeil, J. D. and Janzen, E. D. and McKinnon, J. J. and Landry, D. A.}, year={1994}, pages={825} }
 @article{koritz_livingston_papich_terhune_1994, title={Panel Consensus Report: Human Food Safety: Review of the 1993 Veterinary Drug Bioequivalence Workshop}, volume={17}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Koritz, G.D. and Livingston, R.L. and Papich, M.G. and TerHune, T.}, editor={Martinez, M.N. and Riviere, J.E.Editors}, year={1994}, pages={115–116} }
 @article{raphael_papich_cook_1994, title={Pharmacokinetics of enrofloxacin after a single intramuscular injection in indian star tortoises (Geochelone elegans)}, volume={25}, journal={Journal of Zoo and Wildlife Medicine}, author={Raphael, B.L. and Papich, M. and Cook, R.A.}, year={1994}, pages={88–94} }
 @article{tyczkowska_voyksner_anderson_papich_1994, title={Simultaneous determination of enrofloxacin and its primary metabolite ciprofloxacin in bovine milk and plasma by ion-pairing liquid chromatography}, volume={658}, ISSN={0378-4347}, url={http://dx.doi.org/10.1016/0378-4347(94)00243-6}, DOI={10.1016/0378-4347(94)00243-6}, abstractNote={A simple and sensitive high-performance liquid chromatographic method has been developed for the simultaneous determination of enrofloxacin and ciprofloxacin in bovine milk and plasma. Sample preparation consisted of mixing equal volumes of milk or plasma with acetonitrile-0.1 M sodium hydroxide (1:1, v/v), followed by ultrafiltration through 3000 Da molecular mass cut-off filters. Separation of these two fluoroquinolones in milk or plasma ultrafiltrate was accomplished by ion-pairing liquid chromatography using a reversed-phase analytical column eluted with acetonitrile-methanol-water. Ultraviolet absorbance of the column effluent was monitored over the 230-350 nm range with a photodiode-array detector (lambda max 278 nm). Recoveries of enrofloxacin from bovine milk and plasma were 92-107% and 80-84%, respectively. Recoveries of ciprofloxacin from bovine milk and plasma were 92-105% and 73-75%, respectively. The limit of detection for the two compounds was 5 ng/ml. Enrofloxacin was administered intravenously to a lactating cow at a dose of 2.5 mg/kg. Enrofloxacin was detected in milk within 15 min after injection and the metabolite ciprofloxacin rapidly appeared in plasma and milk. Both enrofloxacin and ciprofloxacin were below the limit of detection (5 ng/ml) by 48 h after drug administration.}, number={2}, journal={Journal of Chromatography B: Biomedical Sciences and Applications}, publisher={Elsevier BV}, author={Tyczkowska, Krystyna L. and Voyksner, Robert D. and Anderson, Kevin L. and Papich, Mark G.}, year={1994}, month={Aug}, pages={341–348} }
 @article{gagnon_ferguson_papich_bailey_1994, title={Single-dose pharmacokinetics of cefazolin in bovine synovial fluid after intravenous regional injection}, volume={17}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.1994.tb00518.x}, DOI={10.1111/j.1365-2885.1994.tb00518.x}, abstractNote={Gagnon, H., Ferguson, J.G., Papich, M.G., Bailey, J.V. Single‐dose pharmacokinetics of cefazolin in bovine synovial fluid after intravenous regional injection. J. vet. Pharmacol. Therap. 17, 31–37.The pharmacokinetic properties of cefazolin in the synovial fluid of the tibiotarsal joint were determined in 10 healthy mature cattle after intravenous regional injection of 2 50 mg cefazolin. A pneumatic tourniquet was positioned proximal to the tibiotarsal joint and the intravenous injection was performed distal to the tourniquet. Synovial fluid concentrations of cefazolin increased in the first 30 mm and fluctuated between 54.7 ± 11.0 &#x006d;̈g/ml (mean ± SEM) and 73.2 ± 13.2 &#x006d;̈g/ml in the following 90 min while the tourniquet remained inflated. After tourniquet removal, synovial fluid concentration‐time curves followed first‐order one‐compartment model decay in most of the animals with an elimination half‐life of 0.82 h (harmonic mean). Therapeutic concentrations of cefazolin in the synovial fluid of normal joints were reached and this injection technique could be used as an alternative to systemic administration of antibiotics to provide adequate concentrations in a localized area.}, number={1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Gagnon, H. and Ferguson, I G. and Papich, M. G. and Bailey, I. V.}, year={1994}, month={Feb}, pages={31–37} }
 @article{papich_korsrud_boison_yates_macneil_janzen_cohen_landry_1993, title={A study of the disposition of procaine penicillin G in feedlot steers following intramuscular and subcutaneous injection}, volume={16}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.1993.tb00178.x}, DOI={10.1111/j.1365-2885.1993.tb00178.x}, abstractNote={The disposition of an aqueous suspension of procaine penicillin G (300 000 U/ mL) was studied in feedlot steers. Four groups of three steers were used. Steers in groups 1 and 2 received procaine penicillin G once daily for 5 days intramuscularly (i.m.) at a dose of 24 000 U/kg (group 1) or of 66 000 U/kg (group 2). The injection on the last day was administered in the gluteal muscle. Steers in group 3 (i.m. neck injection) and group 4 [subcutaneous (s.c.) injection] each received a single dose of procaine penicillin G at a dose of 66 000 U/kg.From every animal, after the last injection in groups 1 and 2 and following the single injection in groups 3 and 4, a series of blood samples was taken at fixed time intervals. The plasma from these samples was analysed for penicillin G by a high performance liquid chromatography (HPLC) assay in order to determine the disposition of penicillin.The maximum plasma concentration (Cmax) and the area under the curve (AUC) were significantly different between groups 1 and 2, but we found no difference in the disappearance rate constant between these two groups. Group 4 single s.c. injections produced a lower mean Cmax (1.85 ± 0.27 ng/mL) than the mean Cmax (4.24 ± 1.08 μg/mL) produced in group 3 by i.m. injections into the neck muscle or the mean Cmax (2.63 ± 0.27 μg/mL) produced in group 2 by i.m. injections into the gluteal muscle. However the mean Cmax produced by i.m. injections into the neck muscles (group 3) was higher than the mean Cmax produced by i.m. injections into the gluteal muscle (group 2). Additionally, the disappearance t½, was longer (18.08 h) in group 4 following the s.c. injection and shorter (8.85 h) in group 3 following the i.m. neck injection, than the t½ following administration of the same dose i.m. into the gluteal muscle (15.96 h) in group 2. In this study, when procaine penicillin G was injected into the gluteal muscle, doses of 66 000 U/kg were necessary to produce plasma concentrations that were above a minimum inhibitory concentration (MIC) for penicillin G of 1.0 μg/mL as compared to doses of 24 000 U/kg.}, number={3}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Papich, M. G. and Korsrud, G. O. and Boison, J. O. and Yates, W. D. G. and Macneil, J. D. and Janzen, E. D. and Cohen, R. D. H. and Landry, D. A.}, year={1993}, month={Sep}, pages={317–327} }
 @article{papich_1993, title={Antiulcer Therapy}, volume={23}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/s0195-5616(93)50301-7}, DOI={10.1016/s0195-5616(93)50301-7}, abstractNote={Perhaps older drugs to treat ulcers, such as antacids, are just as effective as the newer drugs, but veterinarians have all but abandoned these drugs in favor of H2-receptor antagonists, sucralfate, and omeprazole. For most patients, one of the H2-receptor antagonists or sucralfate is probably the initial drug of choice. For patients refractory to these drugs or for which once-a-day dosing is desirable, omeprazole has an advantage. The doses for these drugs are listed in Table 1. Patients presented with acute bleeding ulcers should be managed with emergency therapy. Fluid therapy and blood transfusions are the essential elements of the initial therapy. Surgical resection of the ulcers may be necessary, and most patients should be administered H2-receptor antagonists or sucralfate while they recuperate. Longer term therapy with antiulcer drugs will depend on the predisposing factors that initiated the ulcers. The practice of lavage of the stomach with iced saline or epinephrine to stop bleeding from gastric ulcers is not effective. A common cause of ulcers in small animals is the administration of NSAIDs. Ulcers caused by these agents should be managed like any other ulcers. Fortunately, if ulcers are diagnosed early, they usually heal once the NSAID is discontinued. Unfortunately, many NSAID-induced ulcers identified postmortem did not produce clinical signs, and the ulcers may not be apparent until severe bleeding occurs. In cases in which patients are at risk for developing ulcers from NSAIDs, there may be an advantage in administering the synthetic prostaglandin misoprostol. In many patients that are sensitive to the GI irritation of NSAIDs, switching from one NSAID to another may alleviate some of the signs. Buffered aspirin may be somewhat less irritating than plain uncoated aspirin but will not completely prevent ulcers. The administration of enteric-coated aspirin tablets to dogs is discouraged, because systemic absorption from these tablets is unpredictable.}, number={3}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Papich, Mark G.}, year={1993}, month={May}, pages={497–512} }
 @article{korsrud_boison_papich_yates_macneil_janzen_cohen_landry_lambert_yong_et al._1993, title={Depletion of intramuscularly and subcutaneously injected procaine penicillin G from tissues and plasma of yearling beef steers}, volume={57}, journal={Canadian Journal of Veterinary Research}, author={Korsrud, G.O. and Boison, J.O. and Papich, M.G. and Yates, W.D.G. and MacNeil, J.D. and Janzen, E.D. and Cohen, R.D.H. and Landry, D.A. and Lambert, G. and Yong, M.S. and et al.}, year={1993}, pages={223–230} }
 @article{schlesinger_rubin_papich_hamilton_1993, title={Use of breath hydrogen measurement to evaluate orocecal transit time in cats before and after treatment for hyperthyroidism}, volume={57}, journal={Canadian Journal of Veterinary Research}, author={Schlesinger, D.P. and Rubin, S.I. and Papich, M.G. and Hamilton, D.L.}, year={1993}, pages={89–94} }
 @book{kirk_bonagura_papich_1992, place={Philadelphia}, edition={11th}, title={Current Veterinary Therapy}, publisher={W.B. Saunders Company}, year={1992} }
 @article{boison_korsrud_macneil_keng_papich_1992, title={Determination of penicillin G in bovine plasma by high-performance liquid chromatography after pre-column derivatization}, volume={576}, ISSN={0378-4347}, url={http://dx.doi.org/10.1016/0378-4347(92)80205-5}, DOI={10.1016/0378-4347(92)80205-5}, abstractNote={A simple, selective, and sensitive liquid chromatographic method with ultraviolet detection was developed for the analysis of penicillin G in bovine plasma. The assay utilizes a simple extraction of penicillin G from plasma (with a known amount of penicillin V added as internal standard) with water, dilute sulphuric acid and sodium tungstate solutions, followed by concentration on a conditioned C18 solid-phase extraction column. After elution with 500 microliters of elution solution, the penicillins are derivatized with 500 microliters of 1,2,4-triazole-mercuric chloride solution at 65 degrees C for 30 min. The penicillin-mercury mercaptide complexes are separated by reversed-phase liquid chromatography on a C18 column. The method, which has a detection limit of 5 ng/ml (ppb) in bovine plasma, was used to quantitatively measure the concentrations of penicillin G in plasma of steers at a series of intervals after the intramuscular administration of a commercial formulation of procaine penicillin G.}, number={2}, journal={Journal of Chromatography B: Biomedical Sciences and Applications}, publisher={Elsevier BV}, author={Boison, Joe O. and Korsrud, Gary O. and MacNeil, James D. and Keng, Lily and Papich, Mark}, year={1992}, month={May}, pages={315–320} }
 @article{boison_korsrud_macneil_yates_papich_1992, title={Effect of cold temperature storage on the stability of benzylpenicillin residues in plasma and tissues of food- producing animals}, volume={75}, number={6}, journal={Journal of the Association of Official Analytical Chemists International}, author={Boison, J.O. and Korsrud, G.O. and MacNeil, J.D. and Yates, W.D.G. and Papich, M.G.}, year={1992}, pages={974–978} }
 @inbook{papich_1991, place={Philadelphia}, title={Drugs Used in the Treatment of Gastrointestinal Disease}, booktitle={Consultations in Feline Internal Medicine }, publisher={W.B. Saunders Company}, author={Papich, M.G.}, editor={August, J.R.Editor}, year={1991}, pages={463–469} }
 @article{dow_papich_1991, title={Keeping current on developments in antimicrobial therapy}, journal={Veterinary Medicine}, author={Dow, S.W. and Papich, M.G.}, year={1991}, month={Jun}, pages={600–609} }
 @article{macneil_korsrud_boison_papich_yates_1991, title={Performance of Five Screening Tests for the Detection of Penicillin G Residues in Experimentally Injected Calves}, volume={54}, ISSN={0362-028X}, url={http://dx.doi.org/10.4315/0362-028x-54.1.37}, DOI={10.4315/0362-028x-54.1.37}, abstractNote={Three calves were each injected with a single intramuscular (IM) dose of penicillin G procaine at either 3750, 7500, or 15000 IU per kg of body weight and killed at 24 h postinjection, along with a control calf that had not received penicillin. Tissues were tested by the Swab Test on Premises (STOP), the Calf Antibiotic and Sulfa Test (CAST), the Brilliant Black Reduction Test (BBRT), the Charm Test II, thin layer chromatography - bioautography (TLC/BA), and high performance liquid chromatography (HPLC). Samples of muscle, liver, and kidney from all injected calves contained detectable penicillin residues when analyzed by HPLC. The BBRT and Charm Test II were the most sensitive test kits for penicillin G in muscle, while the Charm Test II also detected residues in livers and kidneys from all injected animals. The STOP and CAST were less sensitive, although improved performance was observed for the STOP using a modified growth medium. Penicillin residues were detected in all livers and kidneys from injected animals using TLC/BA. Urine collected from injected animals 12 and 24 h postinjection was positive by the Live Animal Swab Test (LAST). All urine and tissue samples from the control animal were negative. The BBRT and Charm Test II appear to offer greater sensitivity for penicillin G residues than such currently used procedures as STOP and CAST but should be confirmed by a suitable laboratory method, such as the HPLC procedure used in this study.}, number={1}, journal={Journal of Food Protection}, publisher={International Association for Food Protection}, author={Macneil, J. D. and Korsrud, G. O. and Boison, J. O. and Papich, M. G. and Yates, W. D. G.}, year={1991}, month={Jan}, pages={37–40} }
 @article{papich_1991, title={Therapeutic Drug Monitoring: A Realistic Assessment}, volume={3}, number={2}, journal={Veterinary Medicine Report}, author={Papich, M.G.}, year={1991}, pages={165–171} }
 @article{geor_papich_1990, title={Medical Therapy for Gastrointestinal Ulceration in Foals}, volume={12}, number={3}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Geor, R.J. and Papich, M.G.}, year={1990}, pages={403–413} }
 @article{mawby_meric_crichlow_papich_1990, title={Pharmacological Relaxation of the Urethra in Male Cats: A Study of the Effects of Phenoxybenzamine, Diazepam, Nifedipine, and Xylazine}, volume={55}, journal={Canadian Journal of Veterinary Research}, author={Mawby, D.I. and Meric, S.M. and Crichlow, E.C. and Papich, M.G.}, year={1990}, pages={28–32} }
 @article{papich_1990, title={Tissue Concentrations of Antimicrobials: The Site of Action}, volume={2}, number={2}, journal={Problems in Veterinary Medicine}, author={Papich, M.G.}, year={1990}, pages={312–329} }
 @article{papich_1990, title={Toxicoses from Over-the-Counter Human Drugs}, volume={20}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/s0195-5616(90)50037-6}, DOI={10.1016/s0195-5616(90)50037-6}, abstractNote={This article describes the mechanisms, recognition, and management of toxicoses from human over-the-counter (OTC) drugs. Drugs that have been included were chosen because of their potential for toxicosis and the incidence of exposure. Drug groups discussed are cough, cold, and allergy medications, laxatives and cathartics, antacids, antidiarrheal agents, topicals, and vitamin and iron supplements.}, number={2}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Papich, Mark G.}, year={1990}, month={Mar}, pages={431–451} }
 @article{papich_1989, title={Antiulcer Therapy}, volume={1}, number={3}, journal={Veterinary Medicine Report}, author={Papich, M.G.}, year={1989}, pages={309–320} }
 @article{carrick_papich_middleton_naylor_townsend_1989, title={Clinical and Pathological Effects of Flunixin Meglumine Administration to Neonatal Foals}, volume={53}, number={2}, journal={Canadian Journal of Veterinary Research}, author={Carrick, J.B. and Papich, M.G. and Middleton, D.M. and Naylor, J.M. and Townsend, H.G.G.}, year={1989}, pages={195–201} }
 @inbook{fox_papich_1989, place={Philadelphia}, edition={10th}, title={Complications of Cardiopulmonary Drug Therapy}, booktitle={Current Veterinary Therapy}, publisher={W.B. Saunders Company}, author={Fox, P.R. and Papich, M.G.}, editor={Kirk, R.W.Editor}, year={1989}, pages={308–315} }
 @inbook{papich_1989, place={Philadelphia}, edition={10th}, title={Effects of Drugs on Pregnancy}, booktitle={Current Veterinary Therapy}, publisher={W.B. Saunders Company}, author={Papich, M.G.}, editor={Kirk, R.W.Editor}, year={1989}, pages={1291–1298} }
 @inbook{papich_davis_1989, place={Philadelphia}, edition={10th}, title={Glucocorticoid Therapy}, booktitle={Current Veterinary Therapy}, publisher={W.B. Saunders Company}, author={Papich, M.G. and Davis, L.E.}, editor={Kirk, R.W.Editor}, year={1989}, pages={54–62} }
 @inbook{papich_1989, place={Philadelphia}, edition={10th}, title={Medical Therapy of Gastrointestinal Ulcers}, booktitle={Current Veterinary Therapy}, publisher={W.B. Saunders Company}, author={Papich, M.G.}, editor={Kirk, R.W.Editor}, year={1989}, pages={911–917} }
 @inbook{rubin_papich_1989, place={Philadelphia}, edition={10th}, title={Non-steroidal Anti-inflammatory Drugs}, booktitle={Current Veterinary Therapy}, publisher={W.B. Saunders Company}, author={Rubin, S.I. and Papich, M.G.}, editor={Kirk, R.W.Editor}, year={1989}, pages={47–53} }
 @article{geor_petrie_papich_rosseaux_1989, title={The Protective Effects of Sucralfate and Ranitidine in Foals Experimentally Intoxicated with Phenylbutazone}, volume={53}, number={2}, journal={Canadian Journal of Veterinary Research}, author={Geor, R.J. and Petrie, L. and Papich, M.G. and Rosseaux, C.}, year={1989}, pages={231–238} }
 @article{papich_1988, title={Therapy of Gram-Positive Bacterial Infections}, volume={18}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/s0195-5616(88)50134-1}, DOI={10.1016/s0195-5616(88)50134-1}, abstractNote={This article considers the important features of gram-positive bacteria that relate to chemotherapy and the clinical pharmacology of the drugs of choice for treating these infections.}, number={6}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Papich, Mark G.}, year={1988}, month={Nov}, pages={1267–1285} }
 @article{papich_1988, title={Veterinary Clinics of North America}, volume={18}, number={6}, journal={Clinical Pharmacology}, year={1988} }
 @article{papich_davis_davis_1987, title={Absorption of Salicylate from an Anti-diarrheal Preparation in Dogs and Cats}, volume={23}, journal={Journal of American Animal Hospital Association}, author={Papich, M.G. and Davis, C.A. and Davis, L.E.}, year={1987}, pages={221–226} }
 @article{rubin_papich_1987, title={Acute Renal Failure in Dogs: A case of Gentamicin Toxicity}, volume={9}, journal={Compendium for Continuing Education for the Practicing Veterinarian}, author={Rubin, S.I. and Papich, M.G.}, year={1987}, pages={510–520} }
 @article{papich_1987, title={The Beta-Lactam Antibiotics: Clinical Pharmacology and Recent Developments}, volume={9}, journal={Compendium for Continuing Education}, author={Papich, M.G.}, year={1987}, pages={68–76} }
 @inbook{papich_1986, place={Philadelphia}, edition={9th}, title={Bronchodilator Therapy}, booktitle={Current Veterinary Therapy}, publisher={W.B. Saunders Company}, author={Papich, M.G.}, editor={Kirk, R.W.Editor}, year={1986}, pages={278–284} }
 @article{papich_1986, title={Current Concepts in Pulmonary Pharmacology}, volume={1}, journal={Seminars in Veterinary Medicine and Surgery: Small Animal}, author={Papich, M.G.}, year={1986}, pages={289–301} }
 @article{papich_davis_1986, title={Drug Therapy During Pregnancy and in the Neonate}, volume={16}, ISSN={0195-5616}, url={http://dx.doi.org/10.1016/s0195-5616(86)50058-9}, DOI={10.1016/s0195-5616(86)50058-9}, abstractNote={This article presents important clinical pharmacologic aspects of drug therapy during pregnancy. It reviews the potential adverse effects on the mother and conceptus caused by drugs and includes specific recommendations for therapy. Extensive tables are included that list drugs that are safe and those that are contraindicated during pregnancy.}, number={3}, journal={Veterinary Clinics of North America: Small Animal Practice}, publisher={Elsevier BV}, author={Papich, Mark G. and Davis, Lloyd E.}, year={1986}, month={May}, pages={525–538} }
 @article{papich_neff-davis_davis_mckiernan_brown_1986, title={Pharmacokinetics of Procainamide in Dogs}, volume={47}, journal={American Journal of Veterinary Research}, author={Papich, M.G. and Neff-Davis, C.A. and Davis, L.E. and McKiernan, B.C. and Brown, S.}, year={1986}, pages={2351–2358} }
 @article{papich_davis_davis_1986, title={Procainamide in the Dog: Antiarrhythmic Plasma Concentrations after Intravenous Administration}, volume={9}, DOI={10.1111/j.1365-2885.1986.tb00056.x}, abstractNote={Papich, M.G., Davis, L.E. & Davis, C.A. Procainamide in the dog: antiarrhythmic plasma concentrations after intravenous administration.J, vet. Pharmacol. Therap.9, 359–369.Procainamide hydrochloride was administered to ouabain‐intoxicated dogs to determine an antiarrhythmic plasma concentration of procainamide. Ventricular arrhythmias were produced in dogs following intravenous injections of ouabain. After a sustained ventricular tachycardia was achieved, procainamide was administered and plasma samples collected for assay. Plasma procainamide was assayed by fluorescence polarization immunoassay. Procainamide was administered at increasingly higher constant rate infusions in order to achieve intermittent, steady‐state plasma concentrations. Infusion rates were calculated on the basis of previous pharmacokinetic information.All six dogs that received procainamide converted to a normal sinus cardiac rhythm after attaining a mean plasma concentration of 33.8 μg/ml with a range of 48.5 μg/ml—25.0 μg/ml. It was observed that the computer‐generated prediction of plasma concentrations based upon previous pharmacokinetic data produced an underestimate of the actual plasma concentrations. These data may suggest that plasma concentrations of procainamide for controlling some cardiac arrhythmias in dogs may be higher than plasma concentrations cited for human patients.}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Papich, M.G. and Davis, L.E. and Davis, C.A.}, year={1986}, pages={359–369} }
 @article{papich_davis_1985, title={Drugs and the Liver}, volume={15}, number={1}, journal={Veterinary Clinics of North America (Small Animal Practice)}, author={Papich, M.G. and Davis, L.E.}, year={1985}, pages={63–81} }
 @inbook{papich_1985, place={New York}, edition={2nd}, title={Pharmacokinetics for Some Antimicrobials Used in Small Animals}, booktitle={Veterinary Values}, publisher={Ag. Resources, Inc}, author={Papich, M.G.}, editor={Guin, W.Editor}, year={1985}, pages={203–207} }
 @article{papich_1984, title={Clinical Pharmacology of Cephalosporin Antibiotics}, volume={184}, number={3}, journal={Journal of the American Veterinary Medical Association}, author={Papich, M.G.}, year={1984}, pages={344–347} }