@article{chou_tell_baynes_davis_cheng_maunsell_riviere_lin_2023, title={Development and application of an interactive generic physiologically based pharmacokinetic (igPBPK) model for adult beef cattle and lactating dairy cows to estimate tissue distribution and edible tissue and milk withdrawal intervals for per- and polyfluoroalkyl substances (PFAS)}, volume={181}, ISSN={["1873-6351"]}, DOI={10.1016/j.fct.2023.114062}, abstractNote={Humans can be exposed to per- and polyfluoroalkyl substances (PFAS) through dietary intake from milk and edible tissues from food animals. This study developed a physiologically based pharmacokinetic (PBPK) model to predict tissue and milk residues and estimate withdrawal intervals (WDIs) for multiple PFAS including PFOA, PFOS and PFHxS in beef cattle and lactating dairy cows. Results showed that model predictions were mostly within a two-fold factor of experimental data for plasma, tissues, and milk with an estimated coefficient of determination (R2) of >0.95. The predicted muscle WDIs for beef cattle were <1 day for PFOA, 449 days for PFOS, and 69 days for PFHxS, while the predicted milk WDIs in dairy cows were <1 day for PFOA, 1345 days for PFOS, and zero day for PFHxS following a high environmental exposure scenario (e.g., 49.3, 193, and 161 ng/kg/day for PFOA, PFOS, and PFHxS, respectively, for beef cattle for 2 years). The model was converted to a web-based interactive generic PBPK (igPBPK) platform to provide a user-friendly dashboard for predictions of tissue and milk WDIs for PFAS in cattle. This model serves as a foundation for extrapolation to other PFAS compounds to improve safety assessment of cattle-derived food products.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, author={Chou, Wei-Chun and Tell, Lisa A. and Baynes, Ronald E. and Davis, Jennifer L. and Cheng, Yi-Hsien and Maunsell, Fiona P. and Riviere, Jim E. and Lin, Zhoumeng}, year={2023}, month={Nov} }
 @article{zad_tell_ramachandran_xu_riviere_baynes_lin_maunsell_davis_jaberi-douraki_2023, title={Development of machine learning algorithms to estimate maximum residue limits for veterinary medicines}, volume={179}, ISSN={["1873-6351"]}, DOI={10.1016/j.fct.2023.113920}, abstractNote={Establishing maximum-residue limits (MRLs) for veterinary medicine helps to protect the human food supply. Guidelines for establishing MRLs are outlined by regulatory authorities that drug sponsors follow in each country. During the drug approval process, residue limits are targeted for specific animal species and matrices. Therefore, MRLs are commonly not established for other species. This study demonstrates unestablished MRLs can be reliably predicted for under-represented food commodity groups using machine learning (ML). Classification methods with imbalanced data were used to analyze MRL data from multiple countries by implementing resampling techniques in different ML classifiers. Afterward, we developed and evaluated a data-mining method for predicting unestablished MRLs. Seven different ML classifiers such as support vector classifier, multi-layer perceptron (MLP), random forest, decision tree, k-neighbors, Gaussian NB, and AdaBoost have been selected in this baseline study. Among these, the neural network MLP classifier reliably scored the highest average-weighted F1 score (accuracy >99% with markers and ≈88% without markets) in predicting unestablished MRLs. This provides the first study to apply ML algorithms in regulatory food animal medicine. By predicting and estimating MRLs, we can potentially decrease the use and cost of live animals and the overall research burden of determining new MRLs.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, author={Zad, Nader and Tell, Lisa A. and Ramachandran, Remya Ampadi and Xu, Xuan and Riviere, Jim E. and Baynes, Ronald and Lin, Zhoumeng and Maunsell, Fiona and Davis, Jennifer and Jaberi-Douraki, Majid}, year={2023}, month={Sep} }
 @article{yuan_chou_richards_tell_baynes_davis_riviere_lin_2022, title={A web-based interactive physiologically based pharmacokinetic (iPBPK) model for meloxicam in broiler chickens and laying hens}, volume={168}, ISSN={["1873-6351"]}, DOI={10.1016/j.fct.2022.113332}, abstractNote={Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) commonly used in food-producing animals, including chickens in an extralabel manner. This study aimed to develop a physiologically based pharmacokinetic (PBPK) model for meloxicam in broiler chickens and laying hens to facilitate withdrawal interval (WDI) estimations. The model structure for broiler chickens contained six compartments including plasma, muscle, liver, kidney, fat and rest of body, while an additional compartment of ovary was included for laying hens. The model adequately simulated available pharmacokinetic data of meloxicam in plasma of broiler chickens as well as tissue and egg data of laying hens. The model was converted to a web-based interface and used to predict WDIs following extralabel administrations. The results showed that the estimated WDIs were 50, 44, 11, 3, 3, 22 and 4 days for liver, kidney, muscle, fat, ovary, yolk and white, respectively in laying hens after 14 repeated oral administrations of meloxicam (1 mg/kg) at 24-h intervals. This model provides a useful and flexible tool for risk assessment and management of residues for meat and eggs from chickens treated with meloxicam and will serve as a basis for extrapolation to other NSAID drugs and other poultry species to aid animal-derived food safety assessment.}, journal={FOOD AND CHEMICAL TOXICOLOGY}, author={Yuan, Long and Chou, Wei-Chun and Richards, Emily D. and Tell, Lisa A. and Baynes, Ronald E. and Davis, Jennifer L. and Riviere, Jim E. and Lin, Zhoumeng}, year={2022}, month={Oct} }
 @article{chou_tell_baynes_davis_maunsell_riviere_lin_2022, title={An Interactive Generic Physiologically Based Pharmacokinetic (igPBPK) Modeling Platform to Predict Drug Withdrawal Intervals in Cattle and Swine: A Case Study on Flunixin, Florfenicol, and Penicillin G}, ISSN={["1096-0929"]}, DOI={10.1093/toxsci/kfac056}, abstractNote={Abstract Violative chemical residues in edible tissues from food-producing animals are of global public health concern. Great efforts have been made to develop physiologically based pharmacokinetic (PBPK) models for estimating withdrawal intervals (WDIs) for extralabel prescribed drugs in food animals. Existing models are insufficient to address the food safety concern as these models are either limited to 1 specific drug or difficult to be used by non-modelers. This study aimed to develop a user-friendly generic PBPK platform that can predict tissue residues and estimate WDIs for multiple drugs including flunixin, florfenicol, and penicillin G in cattle and swine. Mechanism-based in silico methods were used to predict tissue/plasma partition coefficients and the models were calibrated and evaluated with pharmacokinetic data from Food Animal Residue Avoidance Databank (FARAD). Results showed that model predictions were, in general, within a 2-fold factor of experimental data for all 3 drugs in both species. Following extralabel administration and respective U.S. FDA-approved tolerances, predicted WDIs for both cattle and swine were close to or slightly longer than FDA-approved label withdrawal times (eg, predicted 8, 28, and 7 days vs labeled 4, 28, and 4 days for flunixin, florfenicol, and penicillin G in cattle, respectively). The final model was converted to a web-based interactive generic PBPK platform. This PBPK platform serves as a user-friendly quantitative tool for real-time predictions of WDIs for flunixin, florfenicol, and penicillin G following FDA-approved label or extralabel use in both cattle and swine, and provides a basis for extrapolating to other drugs and species.}, journal={TOXICOLOGICAL SCIENCES}, author={Chou, Wei-Chun and Tell, Lisa A. and Baynes, Ronald E. and Davis, Jennifer L. and Maunsell, Fiona P. and Riviere, Jim E. and Lin, Zhoumeng}, year={2022}, month={Jun} }
 @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} }
 @misc{lin_li_wang_tell_baynes_davis_vickroy_riviere_2020, title={Physiological parameter values for physiologically based pharmacokinetic models in food-producing animals. Part I: Cattle and swine}, volume={43}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12861}, abstractNote={Abstract Physiologically based pharmacokinetic (PBPK) models for chemicals in food animals are a useful tool in estimating chemical tissue residues and withdrawal intervals. Physiological parameters such as organ weights and blood flows are an important component of a PBPK model. The objective of this study was to compile PBPK‐related physiological parameter data in food animals, including cattle and swine. Comprehensive literature searches were performed in PubMed, Google Scholar, ScienceDirect, and ProQuest. Relevant literature was reviewed and tables of relevant parameters such as relative organ weights (% of body weight) and relative blood flows (% of cardiac output) were compiled for different production classes of cattle and swine. The mean and standard deviation of each parameter were calculated to characterize their variability and uncertainty and to allow investigators to conduct population PBPK analysis via Monte Carlo simulations. Regression equations using weight or age were created for parameters having sufficient data. These compiled data provide a comprehensive physiological parameter database for developing PBPK models of chemicals in cattle and swine to support animal‐derived food safety assessment. This work also provides a basis to compile data in other food animal species, including goats, sheep, chickens, and turkeys.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Lin, Zhoumeng and Li, Miao and Wang, Yu-Shin and Tell, Lisa A. and Baynes, Ronald E. and Davis, Jennifer L. and Vickroy, Thomas W. and Riviere, Jim E.}, year={2020}, month={Sep}, pages={385–420} }
 @article{harris_pickering_boehm_mrisho_davis_2019, title={Comparison of analytical techniques to explain variability in stored drinking water quality and microbial hand contamination of female caregivers in Tanzania}, volume={21}, ISSN={["2050-7895"]}, url={https://doi.org/10.1039/C8EM00460A}, DOI={10.1039/c8em00460a}, abstractNote={Exposure to fecal contamination continues to be a major public health concern for low-income households in sub-Saharan Africa. Drinking water and hands are known transmission routes for pathogens in household environments. In an effort to identify explanatory variables of water and hand contamination, a variety of analytical approaches have been employed that model variation in E. coli contamination as a function of behaviors and household characteristics. Using data collected from 1217 households in Bagamoyo, Tanzania, this investigation compares the explanatory variables identified in the three different modeling methods to explain hand and water contamination: ordinary least squares regression, logistic regression, and classification tree. Although the modeling approaches varied, there were some similarities in the results, with certain explanatory variables being consistently identified as being related to hand and water contamination (e.g., water source type for the water models and activity prior to sampling for the hand models). At the same time, there were also marked differences across the models. In sum, these results suggest there are benefits to using multiple analysis methods to assess relationships in complex systems. The models were also characterized by low explanatory power, suggesting that variation in hand and water contamination is difficult to capture when analyzing one-time water and hand rinse samples. For improved model performance, future studies could explore modeling of repeat measures of water quality and hand contamination.}, number={5}, journal={ENVIRONMENTAL SCIENCE-PROCESSES & IMPACTS}, publisher={Royal Society of Chemistry (RSC)}, author={Harris, Angela R. and Pickering, Amy J. and Boehm, Alexandria B. and Mrisho, Mwifadhi and Davis, Jennifer}, year={2019}, month={May}, pages={893–903} }
 @article{mzyk_bublitz_martinez_davis_baynes_smith_2019, title={Impact of bovine respiratory disease on the pharmacokinetics of danofloxacin and tulathromycin in different ages of calves}, volume={14}, ISSN={["1932-6203"]}, url={http://dx.doi.org/10.1371/journal.pone.0218864}, DOI={10.1371/journal.pone.0218864}, abstractNote={Pneumonia is one of the most economically important respiratory diseases of calves and knowledge of the impact of clinical disease on pharmacokinetics (PK) in young calves is limited. This study was undertaken to investigate the efficacy and PK of two antibiotics, tulathromycin and danofloxacin, in two age groups of calves experimentally infected with Pasteurella multocida. Both danofloxacin, a fluoroquinolone antibiotic, and tulathromycin, a macrolide antibiotic is approved for the treatment of bovine respiratory disease (BRD). To evaluate potential influences of age and disease on drug distribution and elimination in calves, plasma, interstitial fluid (ISF), and pulmonary epithelial lining fluid (PELF) were analyzed for drug concentrations. Concentrations for both drugs in the PELF were estimated by a urea dilution assay of the collected bronchoalveolar lavage fluids. Age was determined to be a significant covariate for calves administered danofloxacin and tulathromycin for plasma PK parameters. For calves administered danofloxacin, the area under the curve (AUC) in the plasma was lower in 6-month old calves (18.9 ± 12.6 hr* μg/mL) vs. 3-week old calves (32.0 ± 8.2 hr* μg/mL). Clearance (CL/F) of danofloxacin was higher in 6-month old calves. In contrast, tulathromycin plasma concentrations were higher in 6 month old calves and CL/F was higher in 3-week old calves. Age did not significantly influence the ISF concentrations of danofloxacin or tulathromycin in calves with respiratory disease, unlike previous studies which reported higher ISF concentrations of danofloxacin and tulathromycin in 6-month old calves when compared to younger calves. PELF concentrations were higher than plasma and ISF for both danofloxacin and tulathromycin, but did not differ between age groups. Potential reasons for age-related differences on plasma concentration–time profiles and the impact of disease on the partitioning of the drug from the blood to the lungs and ISF as a function of age are explored.}, number={6}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Mzyk, Danielle A. and Bublitz, Claire M. and Martinez, Marilyn N. and Davis, Jennifer L. and Baynes, Ronald E. and Smith, Geof W.}, editor={Gladue, DouglasEditor}, year={2019}, month={Jun} }
 @article{li_cheng_chittenden_baynes_tell_davis_vickroy_riviere_lin_2019, title={Integration of Food Animal Residue Avoidance Databank (FARAD) empirical methods for drug withdrawal interval determination with a mechanistic population-based interactive physiologically based pharmacokinetic (iPBPK) modeling platform: example for flunixin meglumine administration}, volume={93}, ISSN={0340-5761 1432-0738}, url={http://dx.doi.org/10.1007/s00204-019-02464-z}, DOI={10.1007/s00204-019-02464-z}, abstractNote={Violative chemical residues in animal-derived food products affect food safety globally and have impact on the trade of international agricultural products. The Food Animal Residue Avoidance Databank program has been developing scientific tools to provide appropriate withdrawal interval (WDI) estimations after extralabel drug use in food animals for the past three decades. One of the tools is physiologically based pharmacokinetic (PBPK) modeling, which is a mechanistic-based approach that can be used to predict tissue residues and WDIs. However, PBPK models are complicated and difficult to use by non-modelers. Therefore, a user-friendly PBPK modeling framework is needed to move this field forward. Flunixin was one of the top five violative drug residues identified in the United States from 2010 to 2016. The objective of this study was to establish a web-based user-friendly framework for the development of new PBPK models for drugs administered to food animals. Specifically, a new PBPK model for both cattle and swine after administration of flunixin meglumine was developed. Population analysis using Monte Carlo simulations was incorporated into the model to predict WDIs following extralabel administration of flunixin meglumine. The population PBPK model was converted to a web-based interactive PBPK (iPBPK) framework to facilitate its application. This iPBPK framework serves as a proof-of-concept for further improvements in the future and it can be applied to develop new models for other drugs in other food animal species, thereby facilitating the application of PBPK modeling in WDI estimation and food safety assessment.}, number={7}, journal={Archives of Toxicology}, publisher={Springer Science and Business Media LLC}, author={Li, Miao and Cheng, Yi-Hsien and Chittenden, Jason T. and Baynes, Ronald E. and Tell, Lisa A. and Davis, Jennifer L. and Vickroy, Thomas W. and Riviere, Jim E. and Lin, Zhoumeng}, year={2019}, month={Apr}, pages={1865–1880} }
 @article{gilbertie_davis_davidson_mcdonald_schirmer_schnabel_2019, title={Oral reserpine administration in horses results in low plasma concentrations that alter platelet biology}, volume={51}, ISSN={["2042-3306"]}, DOI={10.1111/evj.13048}, abstractNote={BACKGROUND
Reserpine is a popular drug in the equine industry for long-term tranquilisation. Clinical observations revealed that blood from horses receiving oral reserpine was hypercoagulable. No studies have documented the pharmacokinetics of orally administered reserpine nor the effects of reserpine on platelets in horses.


OBJECTIVES
To evaluate the pharmacokinetics of oral reserpine in horses and the effects of clinically relevant concentrations of reserpine on platelet functionality in vitro.


STUDY DESIGN
Experimental controlled study.


METHODS
The pharmacokinetics of oral reserpine (2.5 mg/horse, once) were determined in six healthy adult horses. Plasma samples were collected and concentrations of reserpine were determined by UPLC-MS/MS. Using this data, the in vitro effects of reserpine on platelets were examined. Aggregation, adhesion and releasate assays for serotonin and thromboxane B2 were performed on platelets exposed to varying concentrations of reserpine (0.01-10 ng/mL), aspirin (negative control) and saline (unexposed control).


RESULTS
Oral reserpine administration demonstrated low plasma concentrations with a Cmax of 0.2 ± 0.06 ng/mL and a prolonged half-life of 23.6 ± 6.24 h. Simulations over a dose range of 2-8 μg/kg predicted Cmax at steady state between 0.06-0.9 ng/mL. Platelets exposed to these reserpine concentrations in vitro displayed increased aggregation and adhesion compared to unexposed or aspirin-exposed platelets as well as compared to higher concentrations of reserpine. These functional changes correlated with lower concentrations of serotonin and higher concentrations of thromboxane B2 in the platelet suspension supernatant.


MAIN LIMITATIONS
This study used a small number of horses and only in vitro platelet experiments.


CONCLUSIONS
Oral reserpine demonstrates low plasma concentrations and a prolonged half-life in horses. At these concentrations, reserpine causes significant changes in platelet function, most likely due to serotonin release and re-uptake which primes platelets for activation and thromboxane B2 release. These findings suggest that clinicians should harvest blood for biological processing prior to the onset of reserpine administration.}, number={4}, journal={EQUINE VETERINARY JOURNAL}, author={Gilbertie, J. M. and Davis, J. L. and Davidson, G. S. and McDonald, A. M. and Schirmer, J. M. and Schnabel, L. V.}, year={2019}, month={Jul}, pages={537–543} }
 @article{ellis_council-troche_von dollen_beachler_bailey_davis_lyle_2019, title={Pharmacokinetics of Intrarectal Altrenogest in Horses}, volume={72}, ISSN={["1542-7412"]}, DOI={10.1016/j.jevs.2018.10.001}, abstractNote={Hospitalized pregnant mares being held nil per os (PO) because of medical or surgical events present a dilemma for pregnancy maintenance therapy, which commonly includes oral altrenogest. Rectal administration of medications is a recognized route for achieving systemic concentrations, but there are no data on the pharmacokinetics of rectal altrenogest administration in horses. The purpose of this study was to determine the pharmacokinetics of altrenogest following PO or per rectum (PR) administration in mares. Using a randomized two-way crossover study design, six horses received altrenogest (0.088 mg/kg; PO or PR q 24 hours for 5 days), with a 7-day washout period, and the concentrations of altrenogest were determined by an ultrahigh performance liquid chromatography with tandem mass spectrometry. Plasma concentrations persisted above presumed therapeutic concentrations for a mean of 36 hours (range 24-72 hours) and 5.5 hours (range 3-8 hours) for PO and PR administration, respectively. The calculated half-life (T ½) of PO administration (7.01 ± 3.13 hours) was correspondingly increased when compared to PR administration (2.82 ± 1.07 hours). Relative bioavailability of altrenogest following PR administration was only 5.47%. Altrenogest is rapidly absorbed following PR administration in the horse and reaches therapeutic concentrations, making this a viable method of treatment in NPO mares. The decreased bioavailability and shorter detection time suggest 0.088 mg/kg PR q 4-8 hours would be necessary to maintain therapeutic concentrations over a 24-hour period.}, journal={JOURNAL OF EQUINE VETERINARY SCIENCE}, author={Ellis, Katelyn E. and Council-Troche, R. McAlister and Von Dollen, Karen A. and Beachler, Theresa M. and Bailey, C. Scott and Davis, Jennifer L. and Lyle, Sara K.}, year={2019}, month={Jan}, pages={41–46} }
 @article{mzyk_bublitz_hobgood_martinez_davis_smith_baynes_2018, title={Effect of age on plasma protein binding of several veterinary drugs in dairy Check for calves 2}, volume={121}, ISSN={["1532-2661"]}, DOI={10.1016/j.rvsc.2018.09.004}, abstractNote={The intent of this study was to determine what influence, if any, increasing age has on the binding of drugs to plasma proteins in cattle. Plasma from three different cohorts of calves were used. The first group (n = 20) had plasma samples taken at 1, 7 and 21 days of age. These were compared to results from a second group of calves at 8 weeks and third group sampled at 6 months of age. The plasma protein binding of danofloxacin, florfenicol, flunixin meglumine and tulathromycin was determined in vitro via microcentrifugation using three different drug concentrations spiked into the individual plasma samples derived from each calf. Albumin concentrations were lowest at 1 day of age as compared to plasma samples taken from 2 month old and 6 month old calves. There were significant decreases in alpha1-acid glycoprotein in calves until 21 days of age. However, statistically significant age-effects on plasma protein binding were not observed for any of the drugs evaluated in this study. Findings from these calves suggest that age is not an important factor in the binding of these drugs to plasma proteins.}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Mzyk, Danielle A. and Bublitz, Claire M. and Hobgood, Ginger D. and Martinez, Marilyn N. and Davis, Jennifer L. and Smith, Geof W. and Baynes, Ronald E.}, year={2018}, month={Dec}, pages={59–64} }
 @article{martin_clapham_davis_baynes_lin_vickroy_riviere_tell_2018, title={Extralabel drug use in small ruminants}, volume={253}, ISSN={["1943-569X"]}, DOI={10.2460/javma.253.8.1001}, abstractNote={SEARCH AVMA Journals Both journals JAVMA AJVR Advanced Search Saved Searches JAVMA News Classified Ads Register Activate Individual Institution AVMA Home Journals Home Contact Us Help}, number={8}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Martin, Krysta L. and Clapham, Maaike O. and Davis, Jennifer L. and Baynes, Ronald E. and Lin, Zhoumeng and Vickroy, Thomas W. and Riviere, Jim E. and Tell, Lisa A.}, year={2018}, month={Oct}, pages={1001–1009} }
 @article{roth stefaniak_epley_novak_mcandrew_cornell_zhu_mcdaniel_davis_allen_morris_et al._2018, title={Photo-triggered release of 5-fluorouracil from a MOF drug delivery vehicle}, volume={54}, ISSN={1359-7345 1364-548X}, url={http://dx.doi.org/10.1039/C8CC01601A}, DOI={10.1039/C8CC01601A}, abstractNote={A nano metal-organic-framework (nanoMOF) was employed as a first-of-its kind drug delivery vehicle (DDV) for the photo-controlled release of therapeutics with simultaneous breakdown of the carrier into small molecules.}, number={55}, journal={Chemical Communications}, publisher={Royal Society of Chemistry (RSC)}, author={Roth Stefaniak, Kristina and Epley, Charity C. and Novak, Joshua J. and McAndrew, Margaret L. and Cornell, Hannah D. and Zhu, Jie and McDaniel, Dylan K. and Davis, Jennifer L. and Allen, Irving C. and Morris, Amanda J. and et al.}, year={2018}, pages={7617–7620} }
 @article{kjaergaard_davis_acierno_2018, title={Treatment of carprofen overdose with therapeutic plasma exchange in a dog}, volume={28}, ISSN={["1476-4431"]}, DOI={10.1111/vec.12729}, abstractNote={OBJECTIVE
To report the use of therapeutic plasma exchange (TPE) in a dog with carprofen toxicosis.


SUMMARY
A 6-year-old female neutered Bichon Frise weighing 6.9 kg was examined after it had ingested 72 mg/kg carprofen. Mild dehydration without azotemia and with a urine specific gravity of 1.050 was noted at presentation. Treatment consisted of induction of emesis, symptomatic medical therapy, and TPE. The TPE achieved 1.5 plasma volume exchanges over 3 hours. Blood samples and effluent samples were collected every 30 minutes during TPE and additional blood samples were collected 11 and 35 hours after treatment. Carprofen concentrations in these samples were determined by high-pressure liquid chromatography. A 51% reduction in serum carprofen concentration was achieved following TPE.


NEW OR UNIQUE INFORMATION PROVIDED
This report describes the successful reduction of plasma carprofen concentration in a dog using TPE. Although recent studies suggest that this particular dog may not have received a toxic dose, a 51% reduction of plasma carprofen concentration was achieved over 180 minutes, and TPE may be beneficial for treatment of dogs that have ingested higher doses.}, number={4}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={Kjaergaard, Astrid B. and Davis, Jennifer L. and Acierno, Mark J.}, year={2018}, pages={356–360} }
 @article{shrauner_blikslager_davis_campbell_law_lustgarten_prange_2017, title={Feasibility and safety of lumbosacral epiduroscopy in the standing horse}, volume={49}, ISSN={["2042-3306"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84978052421&partnerID=MN8TOARS}, DOI={10.1111/evj.12591}, abstractNote={REASONS FOR PERFORMING STUDY
The large size of the adult horse prevents the use of advanced imaging modalities in most areas of the axial skeleton, including the lumbosacral vertebral column. Traditional imaging techniques are frequently unable to pinpoint the underlying pathology in horses with caudal back pain. In man, lumbosacral epiduroscopy is used to diagnose and treat subjects with chronic back and leg pain. This technique may close the diagnostic gap in horses with similar clinical signs.


OBJECTIVES
To evaluate the safety and feasibility of lumbosacral epiduroscopy in the standing adult horse.


STUDY DESIGN
Descriptive, experimental study.


METHODS
Seven adult horses weighing 504-578 kg were sedated and restrained in stocks in preparation for aseptic surgery. Vascular dilators of increasing size were inserted cranial to the first moveable vertebra caudal to the sacrum to facilitate a minimally invasive approach into the epidural space. A flexible video-endoscope was introduced and advanced as far as its 60-cm working length permitted. Pre-, intra- and post-operative plasma cortisol samples were collected, and neurological and lameness examinations were performed prior to and during the 2 weeks following the procedure. Post-mortem examinations were conducted in 5 of the 7 horses.


RESULTS
Standing lumbosacral epiduroscopy was well tolerated by all horses. The anatomic structures in the epidural space (dura mater, spinal nerve roots, fat and blood vessels) were followed as far cranial as the thoracolumbar region. No complications related to the procedure were noted in the 2-week monitoring period following epiduroscopy. Small, organised haematomas were identified in the sacral epidural space during necropsy in one horse. No abnormalities were seen in the other 4 animals.


CONCLUSIONS
Lumbosacral epiduroscopy can be performed safely in sedated standing horses. The procedure may become a valuable diagnostic tool in horses with caudal back or hindlimb pain of unknown origin.}, number={3}, journal={EQUINE VETERINARY JOURNAL}, author={Shrauner, B. and Blikslager, A. and Davis, J. and Campbell, N. and Law, M. and Lustgarten, M. and Prange, T.}, year={2017}, month={May}, pages={322–328} }
 @misc{davis_2017, title={Nonsteroidal anti-inflammatory drug associated right dorsal colitis in the horse}, volume={29}, ISSN={["2042-3292"]}, DOI={10.1111/eve.12454}, abstractNote={Summary 
Right dorsal colitis in horses is a disease characterised by mucosal ulceration and oedema that is localised to the right dorsal colon. It is considered one of the more severe adverse effects associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly phenylbutazone. Diagnosis is typically made based on a history of NSAID administration, the presence of hypoproteinaemia and hypoalbuminaemia, as well as ultrasound evidence of thickening and oedema of the right dorsal colon wall. Definitive diagnosis is made at surgery or necropsy. Treatment involves discontinuation of NSAID therapy, dietary management, and mucosal protectants such as misoprostol and sucralfate. Prognosis is dependent upon early recognition and appropriate treatment. Horses on prolonged courses of NSAIDs should have frequent monitoring of serum total protein and albumin concentrations, as this is one of the earliest and most consistent clinicopathological findings.}, number={2}, journal={EQUINE VETERINARY EDUCATION}, author={Davis, J. L.}, year={2017}, month={Feb}, pages={104–113} }
 @article{davis_2017, title={Nonsteroidal anti-inflammatory drug associated right dorsal colitis in the horse}, volume={33}, number={4}, journal={Pferdeheilkunde}, author={Davis, J. L.}, year={2017}, pages={403–405} }
 @article{walton_ryan_davis_acierno_2017, title={Treatment of ibuprofen intoxication in a dog via therapeutic plasma exchange}, volume={27}, ISSN={["1476-4431"]}, DOI={10.1111/vec.12608}, abstractNote={OBJECTIVE
To describe the treatment of ibuprofen intoxication with therapeutic plasma exchange in a dog (TPE).


SUMMARY
A 13-year-old male neutered mixed breed dog presented after ingesting approximately 200 mg/kg of ibuprofen. Treatment consisted of supportive medical therapy with IV fluids, gastrointestinal protectants, antiemetics and prostaglandin analogs, and TPE. A cycle of TPE was performed over 180 minutes, achieving 1.5 plasma volume exchanges. During therapy, heparinized blood and effluent samples were collected. Ibuprofen concentrations were determined in the samples by high-pressure liquid chromatography. Post TPE, the dog was continued on supportive medical therapy and was discharged 96 hours after the overdose.


NEW OR UNIQUE INFORMATION
This report describes the use of TPE as an adjunct for ibuprofen intoxication. An 85% reduction in plasma ibuprofen concentration occurred and recovery from a potentially lethal ingestion of ibuprofen was achieved with TPE and supportive care. TPE should be considered when presented with acute ibuprofen intoxication due to the rapid and efficacious nature of therapy.}, number={4}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={Walton, Stuart and Ryan, Kirk A. and Davis, Jennifer L. and Acierno, Mark}, year={2017}, pages={451–457} }
 @article{walton_ryan_davis_acierno_2017, title={Treatment of meloxicam overdose in a dog via therapeutic plasma exchange}, volume={27}, ISSN={["1476-4431"]}, DOI={10.1111/vec.12607}, abstractNote={OBJECTIVE
To describe the treatment of a meloxicam overdose in a dog with therapeutic plasma exchange (TPE).


CASE SUMMARY
A 6-month-old female Bulldog, presented for routine laparoscopic ovariectomy. Postoperatively the dog received an accidental overdose of meloxicam (1 mg/kg IV [intravenously]). The patient was treated with supportive medical therapy and TPE over 210 minutes achieving 1.2 plasma volume exchanges. During therapy, heparinized blood and effluent samples were collected. Meloxicam concentrations were determined in the samples by high pressure liquid chromatography. Post TPE, the dog continued to receive supportive medical therapy and was discharged 48 hours after the overdose. The dog remained asymptomatic for meloxicam intoxication. Follow-up rechecks at 1 and 6 weeks were unremarkable with no further treatment required.


NEW OR UNIQUE INFORMATION
This report describes the successful use of TPE adjunctively following an acute meloxicam overdose. An 82% reduction of plasma meloxicam concentration was achieved over 210 minutes. Twenty-four hours after therapy, a 47% sustained reduction of plasma meloxicam was measured after redistribution of drug between body compartments.}, number={4}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={Walton, Stuart and Ryan, Kirk A. and Davis, Jennifer L. and Acierno, Mark}, year={2017}, pages={444–450} }
 @article{beachler_bailey_mckelvey_davis_edwards_diaw_vasgaard_whitacre_2016, title={Haemoperitoneum in a pregnant mare with an ovarian haematoma}, volume={28}, ISSN={["2042-3292"]}, DOI={10.1111/eve.12211}, abstractNote={Summary 
 
Haemoperitoneum is a rarely reported but life-threatening complication of a multitude of disease processes that can affect horses. This report describes an unusual case of haemoperitoneum in a pregnant mare attributed to a unilateral ovarian haematoma during early gestation. The mare was treated with supportive care and discharged 8 days after initial presentation. Following discharge, the mare maintained her pregnancy to term and delivered a live colt at 321 days of gestation.}, number={7}, journal={EQUINE VETERINARY EDUCATION}, author={Beachler, T. M. and Bailey, C. S. and McKelvey, K. A. and Davis, J. L. and Edwards, A. and Diaw, M. and Vasgaard, J. M. and Whitacre, M. D.}, year={2016}, month={Jul}, pages={359–363} }
 @article{baynes_dedonder_kissell_mzyk_marmulak_smith_tell_gehring_davis_riviere_2016, title={Health concerns and management of select veterinary drug residues}, volume={88}, ISSN={0278-6915}, url={http://dx.doi.org/10.1016/J.FCT.2015.12.020}, DOI={10.1016/J.FCT.2015.12.020}, abstractNote={The aim of this manuscript is to review the potential adverse health effects in humans if exposed to residues of selected veterinary drugs used in food-producing animals. Our other objectives are to briefly inform the reader of why many of these drugs are or were approved for use in livestock production and how drug residues can be mitigated for these drugs. The selected drugs include several antimicrobials, beta agonists, and phenylbutazone. The antimicrobials continue to be of regulatory concern not only because of their acute adverse effects but also because their use as growth promoters have been linked to antimicrobial resistance. Furthermore, nitroimidazoles and arsenicals are no longer approved for use in food animals in most jurisdictions. In recent years, the risk assessment and risk management of beta agonists, have been the focus of national and international agencies and this manuscript attempts to review the pharmacology of these drugs and regulatory challenges. Several of the drugs selected for this review can cause noncancer effects (e.g., penicillins) and others are potential carcinogens (e.g., nitroimidazoles). This review also focuses on how regulatory and independent organizations manage the risk of these veterinary drugs based on data from human health risk assessments.}, journal={Food and Chemical Toxicology}, publisher={Elsevier BV}, author={Baynes, Ronald E. and Dedonder, Keith and Kissell, Lindsey and Mzyk, Danielle and Marmulak, Tara and Smith, Geof and Tell, Lisa and Gehring, Ronette and Davis, Jennifer and Riviere, Jim E.}, year={2016}, month={Feb}, pages={112–122} }
 @article{hooper_korte_giguere_fales_davis_dixon_2016, title={Pharmacokinetics of ceftiofur crystalline-free acid in clinically healthy dogs (Canis lupus familiaris)}, volume={55}, number={2}, journal={Journal of the American Association for Laboratory Animal Science}, author={Hooper, S. E. and Korte, S. W. and Giguere, S. and Fales, W. H. and Davis, J. L. and Dixon, L. W.}, year={2016}, pages={224–229} }
 @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={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{lopez_giguere_berghaus_mullins_davis_2015, title={Pharmacokinetics of danofloxacin and N-desmethyldanofloxacin in adult horses and their concentration in synovial fluid}, volume={38}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12152}, abstractNote={The objectives of this study were to investigate the pharmacokinetics of danofloxacin and its metabolite N-desmethyldanofloxacin and to determine their concentrations in synovial fluid after administration by the intravenous, intramuscular or intragastric routes. Six adult mares received danofloxacin mesylate administered intravenously (i.v.) or intramuscularly (i.m.) at a dose of 5 mg/kg, or intragastrically (IG) at a dose of 7.5 mg/kg using a randomized Latin square design. Concentrations of danofloxacin and N-desmethyldanofloxacin were measured by UPLC-MS/MS. After i.v. administration, danofloxacin had an apparent volume of distribution (mean ± SD) of 3.57 ± 0.26 L/kg, a systemic clearance of 357.6 ± 61.0 mL/h/kg, and an elimination half-life of 8.00 ± 0.48 h. Maximum plasma concentration (Cmax ) of N-desmethyldanofloxacin (0.151 ± 0.038 μg/mL) was achieved within 5 min of i.v. administration. Peak danofloxacin concentrations were significantly higher after i.m. (1.37 ± 0.13 μg/mL) than after IG administration (0.99 ± 0.1 μg/mL). Bioavailability was significantly higher after i.m. (100.0 ± 12.5%) than after IG (35.8 ± 8.5%) administration. Concentrations of danofloxacin in synovial fluid samples collected 1.5 h after administration were significantly higher after i.v. (1.02 ± 0.50 μg/mL) and i.m. (0.70 ± 0.35 μg/mL) than after IG (0.20 ± 0.12 μg/mL) administration. Monte Carlo simulations indicated that danofloxacin would be predicted to be effective against bacteria with a minimum inhibitory concentration (MIC) ≤0.25 μg/mL for i.v. and i.m. administration and 0.12 μg/mL for oral administration to maintain an area under the curve:MIC ratio ≥50.}, number={2}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Lopez, B. S. and Giguere, S. and Berghaus, L. J. and Mullins, M. A. and Davis, J. L.}, year={2015}, month={Apr}, pages={123–129} }
 @article{wong_alcott_davis_hepworth_wulf_coetzee_2015, title={Use of Alprazolam to Facilitate Mare-Foal Bonding in an Aggressive Postparturient Mare}, volume={29}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.12510}, DOI={10.1111/jvim.12510}, abstractNote={A healthy 11-year old, 577 kg maiden Quarter Horse mare was examined at the Lloyd Veterinary Medical Center with a 4-day old colt because the mare would bite or kick the foal when the foal attempted to suckle. The owner bottle fed the foal small amounts of mare’s milk over the first 4 days of life, but the foal became progressively weaker over time and was recumbent and nonresponsive at presentation. Furthermore, although gestational length and parturition were reportedly normal, the mare had apparently not been producing adequate amounts of milk since the foal was born. Upon presentation (Day 1), the foal weighed 36.8 kg and was severely dehydrated, undernourished, unresponsive, hypothermic (32.2°C; reference range [RR], 37.2–38.6°C), bradycardic (40 beats/min; RR, 96–108 beats/min), hypoglycemic (28 mg/dL; RR, 101–226 mg/dL), hyperlactatemic (4.2 mmol/L; RR, <2.5 mmol/L), and had a low serum immunoglobulin G (IgG: 400–800 mg/dL ; RR, >800 mg/dL). A CBC revealed leucopenia (3.41 9 10/lL; RR, 5.1–10.1 9 10/lL) characterized by neutropenia (2.15 9 10/lL; RR, 3.21–8.58 9 10/lL) and relevant serum biochemistry derangements included hypoproteinemia (3.5 g/ dL; RR, 5.3–7.9 g/dL), hypoalbuminemia (1.9 g/dL; RR, 2.8–3.7 g/dL), and hyperbilirubinemia (4.61 mg/ dL; RR, 0.5–3.9 mg/dL). The foal was treated for failure of transfer of passive immunity and polymicrobial sepsis confirmed via blood culture yielding E. coli and Citrobacter sp. Treatment included administration of 2 L of equine plasma, which increased the serum IgG to >800 mg/ dL, fluid resuscitation and treatment, antimicrobial treatment consisting of ceftiofur (Naxel ) (5 mg/kg IV q12h) and gentamicin (10 mg/kg IV q24h) for 10 days followed by sulfamethoxazole-trimethoprim (30 mg/ kg PO q12h) for 7 days, nasoesophageal tube feedings and supportive and nursing care. The mare was treated with domperidone (1.1 mg/kg PO q24h) to increase milk production. The foal was able to ambulate by Day 4 and by Day 6, was bright and alert and attempted to suckle from the mare frequently. However, the mare consistently demonstrated aggressive behavior toward the foal; therefore the mare’s head was tied in a stationary position and periodic sedation (detomidine, Dormosedan, 0.011 mg/kg IM q6h) was administered while the hindlimbs were hobbled to allow the foal to suckle under strict supervision. Although the foal was able to suckle voluntarily, the mare continued to display violent behavior and attempted to bite and kick the foal, but was constrained by the applied restraints. In an attempt to facilitate mare-foal bonding and provide a means for the foal to suckle unsupervised without maternal sedation or restraint, the mare was administered alprazolam (0.035 mg/kg PO q8h) on Day 7. On Day 8, 24 hours after the initial dose of alprazolam, the mare had a quieter demeanor and demonstrated less aggression toward the foal. The next day (Day 9) the mare was not aggressive toward the foal and allowed the foal to suckle regularly. Over the next 2 days, the mare was untied, the hobbles were removed and the foal was allowed to suckle without incident. On Day 11, the mare’s physical examination was within acceptable parameters, but the mare appeared mildly sedate; therefore the frequency of alprazolam administration was decreased to twice daily (0.035 mg/kg PO q12h). On Day 14, the foal weighed 44 kg and was suckling regularly without threat from the mare. The mare and foal were subsequently discharged with instructions to administer alprazolam (0.035 mg/kg PO q12h for 3 days, then 0.018 mg/kg PO q12h for 5 days). One week after discharge the owner reported that the mare demonstrated no aggression toward the foal when suckling, and 6 months after presentation the mare and foal were reportedly healthy. From the Lloyd Veterinary Medical Center, Department of Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA (Wong, Alcott, Hepworth); the Department of Clinical Sciences, North Carolina State University, Raleigh, NC (Davis); and the Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA (Wulf, Coetzee). Corresponding author: D.M. Wong, Lloyd Veterinary Medical Center, Department of Clinical Sciences, Iowa State University, Ames, IA 50011; e-mail: dwong@iastate.edu. Submitted August 4, 2014; Revised October 1, 2014; Accepted October 28, 2014. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. DOI: 10.1111/jvim.12510 Abbreviations:}, number={1}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Wong, D.M. and Alcott, C.J. and Davis, J.L. and Hepworth, K.L. and Wulf, L. and Coetzee, J.H.}, year={2015}, month={Jan}, pages={414–416} }
 @article{davis_kruger_lafevers_barlow_schirmer_breuhaus_2014, title={Effects of quinapril on angiotensin converting enzyme and plasma renin activity as well as pharmacokinetic parameters of quinapril and its active metabolite, quinaprilat, after intravenous and oral administration to mature horses}, volume={46}, ISSN={["2042-3306"]}, DOI={10.1111/evj.12206}, abstractNote={REASONS FOR PERFORMING STUDY
Angiotensin converting enzyme (ACE) inhibitors improve survival and quality of life in human patients and small animals with cardiovascular and renal disease. There is limited information regarding their effects in horses.


OBJECTIVES
The purpose of this study was to determine the pharmacokinetics of quinapril and its effects on ACE and renin in horses.


STUDY DESIGN
Experimental study using healthy mature horses.


METHODS
Six healthy horses were administered quinapril at 120 mg i.v., 120 mg per os and 240 mg per os in a 3-way crossover design. Blood was collected for measurement of quinapril and quinaprilat concentrations using ultra-high pressure liquid chromatography with mass spectrometry. Angiotensin converting enzyme activity and renin activity were measured using a radioenzymatic assay. Noncompartmental pharmacokinetic modelling and statistical analyses were performed.


RESULTS
No adverse effects were observed during the study period. Intravenous and oral administration significantly inhibited ACE activity. Renin concentrations increased in all groups, but this increase was not statistically significant. Following i.v. administration of quinapril, mean terminal half-life was 0.694 h and 1.734 h for quinapril and quinaprilat, respectively. The mean volume of distribution and clearance for quinapril were 0.242 l/kg bwt and 11.93 ml/kg bwt/min, respectively. Maximum concentration for quinaprilat was 145 ng/ml at 0.167 h. Bioavailability of quinapril following oral administration was <5%. Quinaprilat was detected in all horses following oral administration of quinapril; however, it was below the limit of quantification of the assay (2.5 ng/ml) for most horses in the 120 mg dosing group.


CONCLUSIONS
These results suggest that, despite low plasma concentrations, quinapril has sufficient oral absorption to produce inhibition of ACE in healthy horses. Controlled studies in clinically affected horses are indicated. Quinapril provides a potential treatment alternative for horses with cardiovascular and renal disease.}, number={6}, journal={EQUINE VETERINARY JOURNAL}, author={Davis, J. L. and Kruger, K. and LaFevers, D. H. and Barlow, B. M. and Schirmer, J. M. and Breuhaus, B. A.}, year={2014}, month={Nov}, pages={729–733} }
 @article{holland_fogle_blikslager_curling_barlow_schirmer_davis_2014, title={Pharmacokinetics and pharmacodynamics of three formulations of firocoxib in healthy horses}, volume={38}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12177}, DOI={10.1111/jvp.12177}, abstractNote={The objectives of this study were to compare the pharmacokinetics and COX selectivity of three commercially available formulations of firocoxib in the horse. Six healthy adult horses were administered a single dose of 57 mg intravenous, oral paste or oral tablet firocoxib in a three-way, randomized, crossover design. Blood was collected at predetermined times for PGE2 and TXB2 concentrations, as well as plasma drug concentrations. Similar to other reports, firocoxib exhibited a long elimination half-life (31.07 ± 10.64 h), a large volume of distribution (1.81 ± 0.59L/kg), and a slow clearance (42.61 ± 11.28 mL/h/kg). Comparison of the oral formulations revealed a higher Cmax , shorter Tmax , and greater AUC for the paste compared to the tablet. Bioavailability was 112% and 88% for the paste and tablet, respectively. Maximum inhibition of PGE2 was 83.76% for the I.V. formulation, 52.95% for the oral paste formulation, and 46.22% for the oral tablet formulation. Pharmacodynamic modeling suggests an IC50 of approximately 27 ng/mL and an IC80 of 108 ng/ mL for COX2 inhibition. Inhibition of TXB2 production was not detected. This study indicates a lack of bioequivalence between the oral formulations of firocoxib when administered as a single dose to healthy horses.}, number={3}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Holland, B. and Fogle, C. and Blikslager, A. T. and Curling, A. and Barlow, B. M. and Schirmer, J. and Davis, J. L.}, year={2014}, month={Nov}, pages={249–256} }
 @article{wong_davis_alcott_hepworth-warren_galow-kersh_rice_coetzee_2014, title={Pharmacokinetics and physiologic effects of alprazolam after a single oral dose in healthy mares}, volume={38}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12192}, DOI={10.1111/jvp.12192}, abstractNote={The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α-hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one-compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of alprazolam were as follows: Cmax 14.76 ± 3.72 ng/mL and area under the curve (AUC0-∞ ) 358.77 ± 76.26 ng·h/mL. Median (range) Tmax was 3 h (1-12 h). Alpha-hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (Cmax 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted.}, number={3}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Wong, D. M. and Davis, J. L. and Alcott, C. J. and Hepworth-Warren, K. L. and Galow-Kersh, N. L. and Rice, S. and Coetzee, J. F.}, year={2014}, month={Nov}, pages={301–304} }
 @article{hovanessian_davis_mckenzie_hodgson_hodgson_crisman_2014, title={Pharmacokinetics and safety of firocoxib after oral administration of repeated consecutive doses to neonatal foals}, volume={37}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12082}, abstractNote={The purpose of this study was to determine the pharmacokinetics and safety profile of firocoxib in neonatal foals. Seven healthy foals were administered 0.1 mg/kg firocoxib orally q24 h for nine consecutive days, commencing at 36 h of age. Blood was collected for firocoxib analysis using high-pressure liquid chromatography with fluorescence detection at 0 (dose #1 only), 0.25, 0.5, 1, 2, 4, 8, 16, and 24 h after doses 1, 5, and 9. For all other doses (2, 3, 4, 6, 7, and 8), blood was collected immediately prior to the next dose (24 h trough). Elimination samples (36, 48, 72, 96, 120, and 144 h) were collected after dose 9. Safety was assessed via physical examinations, body weight measurements, gastroscopy, complete blood count, plasma biochemistry and urinalysis. Firocoxib was rapidly absorbed following oral administration with minimal accumulation after repeat dosing. After the final dose, the terminal half-life was approximately 11 h. Firocoxib was below the limit of detection (<2.5 ng/mL) in plasma 72 h after the final dose. No significant abnormalities were found on blood analyses, urinalysis, or gastroscopy. This study demonstrated that firocoxib is absorbed in neonatal foals with no demonstrable adverse effects after repeated doses of 0.1 mg/kg.}, number={3}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Hovanessian, N. and Davis, J. L. and McKenzie, H. C. and Hodgson, J. L. and Hodgson, D. R. and Crisman, M. V.}, year={2014}, month={Jun}, pages={243–251} }
 @article{fultz_giguere_berghaus_davis_2014, title={Plasma and pulmonary pharmacokinetics of desfuroylceftiofur acetamide after weekly administration of ceftiofur crystalline free acid to adult horses}, volume={46}, ISSN={["2042-3306"]}, DOI={10.1111/evj.12107}, abstractNote={REASONS FOR PERFORMING STUDY
Current labelling for the use of ceftiofur crystalline free acid (CCFA) in horses states that 2 i.m. doses must be administered 4 days apart to provide 10 days of therapeutic coverage. A 10 day treatment regimen is not sufficient for the long-term treatment of horses with severe lung consolidation or pleuropneumonia. There are currently no data to guide an appropriate dosing interval when a longer treatment regimen is warranted.


OBJECTIVES
To determine steady-state plasma and pulmonary epithelial lining fluid (PELF) concentrations of desfuroylceftiofur acetamide (DCA) after weekly i.m. administration of CCFA to adult horses.


STUDY DESIGN
Experimental study.


METHODS
Seven adult horses received i.m. CCFA at a dose of 6.6 mg/kg bwt on Day 0, Day 4 and every 7 days thereafter for 3 additional doses. Concentrations of DCA in plasma and PELF were measured at various time intervals.


RESULTS
After weekly i.m. administration, the mean (± s.d.) steady-state peak DCA concentration in plasma (2.87 ± 1.50 μg/ml) was significantly higher than that in PELF (0.84 ± 0.53 μg/ml). Mean terminal half-lives in plasma (77.5 ± 17.5 h) and PELF (92.8 ± 59.0 h) were not significantly different. Concentrations of DCA in plasma and PELF remained in the therapeutic range for the entire dosing interval.


CONCLUSIONS
After the initial 2-dose regimen 4 days apart, weekly i.m. administration of CCFA was well tolerated and resulted in plasma and PELF DCA concentrations above the minimal inhibitory concentration that inhibits growth of at least 90% of common lower respiratory tract pathogens of horses.


POTENTIAL RELEVANCE
Weekly administration of CCFA would appear appropriate when a treatment regimen longer than 10 days is warranted based on clinical signs and disease severity.}, number={2}, journal={EQUINE VETERINARY JOURNAL}, author={Fultz, L. and Giguere, S. and Berghaus, L. J. and Davis, J. L.}, year={2014}, month={Mar}, pages={252–255} }
 @article{caniglia_davis_schott_brakenhoff_2014, title={Septic funiculitis caused by Streptococcus equi subspecies equi infection with associated immune- mediated haemolytic anaemia}, volume={26}, ISSN={["2042-3292"]}, DOI={10.1111/eve.12116}, abstractNote={Summary 
 
A 2-year-old Quarter Horse gelding presented for anaemia, icterus, depression and intermittent colic 2 weeks after routine castration. Bilateral septic funiculitis with Streptoccocus equi ssp. equi with secondary immune-mediated haemolytic anaemia were diagnosed. A blood transfusion was required to facilitate general anaesthesia for surgical excision of the septic funiculitis. Antibiotic therapy was provided initially with chloramphenicol and later enrofloxacin. Immunosuppressive therapy was provided with dexamethasone and later azathioprine. The horse responded well to treatment and was discharged 8 weeks after presentation. Streptococcus equi ssp. equi should be considered in cases with septic funiculitis and the potential for a secondary immune-mediated haemolytic anaemia exists with this bacterial species.}, number={5}, journal={EQUINE VETERINARY EDUCATION}, author={Caniglia, C. J. and Davis, J. L. and Schott, H. C., III and Brakenhoff, J. E.}, year={2014}, month={May}, pages={227–233} }
 @article{fultz_giguere_berghaus_davis_2013, title={Comparative pharmacokinetics of desfuroylceftiofur acetamide after intramuscular versus subcutaneous administration of ceftiofur crystalline free acid to adult horses}, volume={36}, ISSN={["0140-7783"]}, DOI={10.1111/jvp.12030}, abstractNote={Ceftiofur crystalline free acid (CCFA) is approved by the U.S. Food and Drug Administration Center for Veterinary Medicine for treatment of lower respiratory tract infections in horses caused by susceptible strains of Streptococcus equi subspecies zooepidemicus. Ceftiofur, administered as either ceftiofur sodium or CCFA, is rapidly metabolized to desfuroylceftiofur (Jaglan et al., 1994). The in vitro activity of desfuroylceftiofur against common gram-negative pathogens and streptococci is almost identical to that of ceftiofur (Salmon et al., 1996). Current labeling for the use of CCFA in horses states that two intramuscular (IM) doses must be administered 4 days apart. This regimen is designed to provide concentrations of ceftiofur and desfuroylceftiofur-related metabolites in plasma above the therapeutic target of 0.2 lg/mL for a minimum of 10 days from the beginning of treatment. This threshold of 0.2 lg/mL is above the minimum inhibitory concentration that inhibits growth of at least 90% (MIC90) of S. equi subspecies zooepidemicus isolates (Jaglan et al., 1994; Bade et al., 2009). To allow slow and sustained release of the drug, CCFA is in a caprylic/capric triglyceride and cottonseed oil-based suspension. An oil-based suspension is more likely to be irritating to surrounding muscles than the sterile aqueous solution used for the ceftiofur sodium formulation. In a recent study, self-limiting injection site swelling was reported in 10 of 278 (3.6%) horses treated with IM CCFA (McClure et al., 2011). In some horses, the IM injection site reaction can be quite large and very painful. In a recent study, administration of CCFA to newborn foals by the subcutaneous (SC) route did not result in swelling or pain at the site of injection (Hall et al., 2011). Administration of Excede to adult horses by the SC route might minimize injection site irritation and facilitate administration. However, because the entire dosage regimen depends on only two administrations, alterations in the pharmacokinetic profile as a result giving the dose SC could affect efficacy. The main objective of the present study was to compare the pharmacokinetic profile of CCFA administered by the SC route to that achieved after administration by the IM route. In addition, we sought to compare the size of visible injection site swellings after administration by the two routes of administration. We hypothesized that SC administration of CCFA to adult horses will be well tolerated and result in therapeutic plasma concentrations. Twelve barren adult mares (7–17 years of age) ranging in weight from 471 to 675 kg were used in the study. Horses were randomly assigned into two treatment groups. Ceftiofur crystalline free acid (CCFA; Excede, Pfizer Animal Health, Kalamazoo, MI, USA) was administered to each horse at a total dose of 6.6 mg/kg of body weight on day 0 and again on day 4. Six horses received half of the calculated volume SC on each side of the neck. Six other horses received half of the calculated volume IM on each side of the neck. The volume of drug administered at each injection site ranged from 7.8 to 11.1 mL. All injections were performed using an 18-gauge 1.5-inch needle. Blood samples (10 mL) were obtained by jugular venipuncture 0, 0.5, 1, 2, 4, 6, 8, 12, 24, and 48 h after administration of the drug on day 0 and on day 4. Additionally, blood samples were collected on day 8 and on day 10 of the study. Blood samples were centrifuged and plasma was stored at 80°C until analysis. The sites of injection were monitored daily for visible swelling by a nonblinded investigator. When injection site swelling was detected, the horizontal and vertical diameters of each site of swelling were measured using Vernier calipers. For each side of the neck, the surface area of each visible swelling was estimated by multiplying the horizontal diameter by the vertical diameter. On a given day, the total surface area was obtained by adding the surface areas from swellings on each side of the neck. The number of days a given area of swelling at an injection site was detectable was also recorded. Ceftiofur and desfuroylceftiofur metabolites in plasma samples and standards were derivitazed to desfuroylceftiofur acetamide (DCA) and then subjected to solid-phase extraction}, number={3}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Fultz, L. and Giguere, S. and Berghaus, L. J. and Davis, J. L.}, year={2013}, month={Jun}, pages={309–312} }
 @article{kruger_davis_2013, title={Management and complications associated with treatment of cervical oesophageal perforations in horses}, volume={25}, ISSN={["2042-3292"]}, DOI={10.1111/eve.12020}, abstractNote={Summary 
 
Six horses were evaluated for colic and anorexia, choke or suspected oesophageal rupture with and without tracheal laceration. Clinical findings were variable, but a painful ventral neck swelling was noted in all cases. Two of the horses had signs of dehydration and sepsis. Additional findings included evidence of previous trauma over the trachea and oesophagus, ventral neck abscessation, choke and aspiration pneumonia. A diagnosis of oesophageal perforation was made using endoscopy. Two horses were subjected to euthanasia without treatment. All horses where treatment was attempted received debridement of the oesophageal perforation and surrounding tissues with or without surgical closure of the oesophageal defect. Other therapies included broad spectrum antimicrobials, anti-inflammatory drugs, fluid and nutritional support as well as additional therapeutics for sepsis and individual complications. Complications included diverticulum formation, thrombophlebitis, diarrhoea, laryngeal hemiplegia, azotaemia, aspiration pneumonia, oesophageal obstruction, weight loss and laminitis. All 4 treated horses recovered from the oesophageal perforation and are able to eat a normal diet. Two of the 4 horses have had infrequent episodes of recurrent choke. Oesophageal rupture should be considered as a differential diagnosis for horses with a painful swelling of the ventral neck. With surgical debridement and adequate supportive care, oesophageal perforation cases can have a fair to good long-term survival, although chronic complications can occur, therapy is prolonged, and a significant economic commitment is required.}, number={5}, journal={EQUINE VETERINARY EDUCATION}, author={Kruger, K. and Davis, J. L.}, year={2013}, month={May}, pages={247–255} }
 @article{wearn_davis_hodgson_raffetto_crisman_2013, title={Pharmacokinetics of a continuous rate infusion of ceftiofur sodium in normal foals}, volume={36}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2012.01403.x}, abstractNote={[Extract] Systemic bacterial infection, resulting in bacterial sepsis and systemic inflammatory response syndrome, is the primary cause of equine neonatal morbidity and mortality (Cohen, 1994; Hollis et al., 2008). Ceftiofur sodium (CS), a third-generation cephalosporin antimicrobial, has in vitro efficacy against many bacterial organisms cultured from septicemic equine neonates (Jaglan et al., 1994; Marsh & Palmer, 2001; Sanchez et al., 2008; Meyer et al., 2009). 
 
Ceftiofur sodium is a time-dependent, bactericidal, β-lactam antimicrobial (Owens & Ambrose, 2007). To optimize the likelihood of efficacy, dosing regimens are designed to maximize the duration concentrations of antimicrobial at the site of infection are greater than the MIC of the pathogen (Turnidge, 1998). For gram-positive organisms, CS has a period of post-antibiotic effect and post-antibiotic leukocyte enhancement. For gram-negative organisms no post-antibiotic effect exists and reduced efficacy of cephalosporin antimicrobial therapy has been reported when T > MIC is MIC for 90–100% of the dosing interval is recommended (Turnidge, 1998).}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Wearn, J. M. G. and Davis, J. L. and Hodgson, D. R. and Raffetto, J. A. and Crisman, M. V.}, year={2013}, month={Feb}, pages={99–101} }
 @article{newman_prange_jennings_barlow_davis_2013, title={Pharmacokinetics of tobramycin following intravenous, intramuscular, and intra-articular administration in healthy horses}, volume={36}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12048}, abstractNote={The objectives of this study were to examine the pharmacokinetics of tobramycin in the horse following intravenous (IV), intramuscular (IM), and intra-articular (IA) administration. Six mares received 4 mg/kg tobramycin IV, IM, and IV with concurrent IA administration (IV+IA) in a randomized 3-way crossover design. A washout period of at least 7 days was allotted between experiments. After IV administration, the volume of distribution, clearance, and half-life were 0.18 ± 0.04 L/kg, 1.18 ± 0.32 mL·kg/min, and 4.61 ± 1.10 h, respectively. Concurrent IA administration could not be demonstrated to influence IV pharmacokinetics. The mean maximum plasma concentration (Cmax ) after IM administration was 18.24 ± 9.23 μg/mL at 1.0 h (range 1.0-2.0 h), with a mean bioavailability of 81.22 ± 44.05%. Intramuscular administration was well tolerated, despite the high volume of drug administered (50 mL per 500 kg horse). Trough concentrations at 24 h were below 2 μg/mL in all horses after all routes of administration. Specifically, trough concentrations at 24 h were 0.04 ± 0.01 μg/mL for the IV route, 0.04 ± 0.02 μg/mL for the IV/IA route, and 0.02 ± 0.02 for the IM route. An additional six mares received IA administration of 240 mg tobramycin. Synovial fluid concentrations were 3056.47 ± 1310.89 μg/mL at 30 min after administration, and they persisted for up to 48 h with concentrations of 14.80 ± 7.47 μg/mL. Tobramycin IA resulted in a mild chemical synovitis as evidenced by an increase in synovial fluid cell count and total protein, but appeared to be safe for administration. Monte Carlo simulations suggest that tobramycin would be effective against bacteria with a minimum inhibitory concentration (MIC) of 2 μg/mL for IV administration and 1 μg/mL for IM administration based on Cmax :MIC of 10.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Newman, J. C. and Prange, T. and Jennings, S. and Barlow, B. M. and Davis, J. L.}, year={2013}, month={Dec}, pages={532–541} }
 @article{davis_yi_salmon_charlton_colitz_gilger_2012, title={Sustained-Release Celecoxib from Incubated Acrylic Intraocular Lenses Suppresses Lens Epithelial Cell Growth in an Ex Vivo Model of Posterior Capsule Opacity}, volume={28}, ISSN={["1080-7683"]}, DOI={10.1089/jop.2011.0196}, abstractNote={PURPOSE
To determine whether celecoxib (CXB) can be released from incubated intraocular lenses (IOLs) sufficiently to inhibit lens epithelial cell (LEC) growth in an ex vivo model of posterior capsule opacification (PCO).


MATERIALS
LEC growth was evaluated for 14 days in canine lens capsules (LCs) that had been exposed to media containing 20 μM CXB for 1-5 days. After the incubation of hydrophilic and hydrophobic IOLs in CXB solution, the determination of the in vitro release of CXB from the IOLs was performed for up to 28 days. The incubated and nonincubated IOLs were evaluated in the ex vivo model of PCO, and the rate of LEC growth was evaluated over 28 days.


RESULTS
The treatment of LCs with 20 μM CXB for 4 and 5 days completely inhibited LEC growth. LEC repopulation did not occur after the removal of CXB. IOLs incubated in CXB for 24 h resulted in a sustained release of CXB in vitro at levels theoretically sufficient to inhibit PCO. LCs in the ex vivo model of PCO treated with acrylic IOLs incubated in CXB had significantly suppressed LEC ingrowth compared with untreated and IOL-only LCs.


CONCLUSIONS
A 4-day treatment of LCs with a concentration of 20 μM CXB may effectively prevent PCO. IOLs incubated in CXB for 24 h resulted in a sustained release of CXB in vitro at levels sufficient to inhibit LEC growth in the ex vivo model of PCO. Further studies are needed to determine whether CXB-incubated IOLs can effectively prevent the development of PCO in vivo.}, number={4}, journal={JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS}, author={Davis, Jennifer L. and Yi, Na Young and Salmon, Jacklyn H. and Charlton, Anna N. and Colitz, Carmen M. H. and Gilger, Brian C.}, year={2012}, month={Aug}, pages={359–368} }
 @article{clode_davis_davidson_salmon_lafevers_gilger_2011, title={Aqueous humor and plasma concentrations of a compounded 0.2% solution of terbinafine following topical ocular administration to normal equine eyes}, volume={14}, ISSN={1463-5216}, url={http://dx.doi.org/10.1111/j.1463-5224.2010.00841.x}, DOI={10.1111/j.1463-5224.2010.00841.x}, abstractNote={OBJECTIVE
To determine the transcorneal penetration and systemic absorption of a compounded 0.2% terbinafine solution following repeated topical administration to normal equine eyes. Sample population  Six healthy adult horses with normal ocular examinations.


PROCEDURES
One eye of each horse received 0.2 mL of a compounded 0.2% terbinafine solution every 4 h for seven doses. During the 1 h following administration of the final dose, multiple peripheral blood samples were obtained, and a single aqueous humor (AH) sample was collected at the end of the hour. AH and plasma concentrations of terbinafine were determined using high pressure liquid chromatography (HPLC). Stability of the formulation was assessed with HPLC analysis over a 14-day time period.


RESULTS
Terbinafine was not detected in the AH or plasma of any horse at any time point. No signs of ocular irritation or systemic toxicity were noted in any horse at any time point. The solution was stable over 14 days.


CONCLUSION
Topical ocular administration of compounded 0.2% terbinafine solution does not result in detectable AH or plasma levels following administration to normal equine eyes, suggesting its use for deep corneal or intraocular fungal infections in equine ophthalmology may be limited.}, number={1}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Clode, Alison and Davis, Jennifer and Davidson, Gigi and Salmon, Jacklyn and Lafevers, Heath and Gilger, Brian}, year={2011}, month={Jan}, pages={41–47} }
 @article{alcott_sponseller_wong_davis_soliman_wang_hsu_2011, title={Clinical and Immunomodulating Effects of Ketamine in Horses with Experimental Endotoxemia}, volume={25}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2011.0749.x}, abstractNote={BACKGROUND
Ketamine has immunomodulating effects both in vitro and in vivo during experimental endotoxemia in humans, rodents, and dogs.


HYPOTHESIS
Subanesthetic doses of ketamine will attenuate the clinical and immunologic responses to experimental endotoxemia in horses.


ANIMALS
Nineteen healthy mares of various breeds.


METHODS
Experimental study. Horses were randomized into 2 groups: ketamine-treated horses (KET; n = 9) and saline-treated horses (SAL; n = 10). Both groups received 30 ng/kg of lipopolysaccharide (LPS, Escherichia coli, O55:B5) 1 hour after the start of a continuous rate infusion (CRI) of racemic ketamine (KET) or physiologic saline (SAL). Clinical and hematological responses were documented and plasma concentrations of tumor necrosis factor-α (TNF-α) and thromboxane B(2) (TXB(2)) were quantified.


RESULTS
All horses safely completed the study. The KET group exhibited transient excitation during the ketamine loading infusion (P < .05) and 1 hour after discontinuation of administration (P < .05). Neutrophilic leukocytosis was greater in the KET group 8 and 24 hours after administration of LPS (P < .05). Minor perturbations of plasma biochemistry results were considered clinically insignificant. Plasma TNF-α and TXB(2) production peaked 1.5 and 1 hours, respectively, after administration of LPS in both groups, but a significant difference between treatment groups was not demonstrated.


CONCLUSIONS AND CLINICAL IMPORTANCE
A subanesthetic ketamine CRI is well tolerated by horses. A significant effect on the clinical or immunologic response to LPS administration, as assessed by clinical observation, hematological parameters, and TNF-α and TXB(2) production, was not identified in healthy horses with the subanesthetic dose of racemic ketamine utilized in this study.}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Alcott, C. J. and Sponseller, B. A. and Wong, D. M. and Davis, J. L. and Soliman, A. M. and Wang, C. and Hsu, W.}, year={2011}, pages={934–943} }
 @article{boyle_hawkins_davis_robertson_2011, title={Failure of nebulized irritant, acidic, or hypotonic solutions or external mechanical stimulation of the trachea to consistently induce coughing in healthy, awake dogs}, volume={75}, number={3}, journal={Canadian Journal of Veterinary Research}, author={Boyle, T. E. and Hawkins, E. C. and Davis, J. L. and Robertson, I. D.}, year={2011}, pages={228–232} }
 @article{messenger_davis_lafevers_barlow_posner_2011, title={Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site}, volume={38}, ISSN={["1467-2995"]}, DOI={10.1111/j.1467-2995.2011.00613.x}, abstractNote={OBJECTIVE
To describe the pharmacokinetics and adverse effects of intravenous (IV) and sublingual (SL) buprenorphine in horses, and to determine the effect of sampling site on plasma concentrations after SL administration.


STUDY DESIGN
Randomized crossover experiment; prospective study.


ANIMALS
Eleven healthy adult horses between 6 and 20 years of age and weighing 487-592 kg.


METHODS
In the first phase; buprenorphine was administered as a single IV or SL dose (0.006 mg kg(-1)) and pharmacokinetic parameters were determined for each route of administration using a noncompartmental model. In the second phase; the jugular and lateral thoracic veins were catheterized for simultaneous venous blood sampling, following a dose of 0.006 mg kg(-1) SL buprenorphine. For both phases, plasma buprenorphine concentrations were measured using ultra-performance liquid chromatography with mass spectrometry. At each sampling period, horses were assessed for behavioral excitement and gastrointestinal motility.


RESULTS
Following IV administration, buprenorphine mean ± SD half-life was 5.79 ± 1.09 hours. Systemic clearance (Cl) following IV administration was 6.13 ± 0.86 mL kg(-1) minute(-1) and volume of distribution at steady-state was 3.16 ± 0.65 L kg(-1). Following IV administration, horses showed signs of excitement. Gastrointestinal sounds were decreased following both routes of administration; however, none of the horses exhibited signs of colic. There was a significant discrepancy between plasma buprenorphine concentrations measured in the jugular vein versus the lateral thoracic vein following phase 2, thus pharmacokinetic parameters following SL buprenorphine are not reported.


CONCLUSIONS AND CLINICAL RELEVANCE
Buprenorphine has a long plasma half-life and results in plasma concentrations that are consistent with analgesia in other species for up to 4 hours following IV administration of this dose in horses. While buprenorphine is absorbed into the circulation following SL administration, jugular venous sampling gave a false measurement of the quantity absorbed and should not be used to study the uptake from SL administration.}, number={4}, journal={VETERINARY ANAESTHESIA AND ANALGESIA}, author={Messenger, Kristen M. and Davis, Jennifer L. and LaFevers, Douglas H. and Barlow, Beth M. and Posner, Lysa P.}, year={2011}, month={Jul}, pages={374–384} }
 @article{wong_davis_white_2011, title={Motility of the equine gastrointestinal tract: Physiology and pharmacotherapy}, volume={23}, ISSN={["2042-3292"]}, DOI={10.1111/j.2042-3292.2010.00173.x}, abstractNote={Summary Normal gastrointestinal (GI) motility patterns are necessary to maintain transit of ingesta and to facilitate digestion and absorption of nutrients. Disorders of the equine GI tract are frequently encountered by the equine practitioner and these disorders are often associated with an interruption in normal intestinal motility patterns, thus complicating treatment of the primary disease. Consequently, numerous treatments have been investigated in horses to facilitate the return of normal intestinal motility. The purpose of this article is to provide a brief review of the anatomy and physiology of the GI tract in the horse and review medications available to the equine veterinarian that may potentially promote intestinal motility.}, number={2}, journal={EQUINE VETERINARY EDUCATION}, author={Wong, D. M. and Davis, J. L. and White, N. A.}, year={2011}, month={Feb}, pages={88–100} }
 @article{davis_messenger_lafevers_barlow_posner_2011, title={Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse}, volume={35}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2011.01284.x}, abstractNote={The purpose of this study was to determine the pharmacokinetics of buprenorphine following intravenous (i.v.) and intramuscular (i.m.) administration in horses. Six horses received i.v. or i.m. buprenorphine (0.005 mg/kg) in a randomized, crossover design. Plasma samples were collected at predetermined times and horses were monitored for adverse reactions. Buprenorphine concentrations were measured using ultra-performance liquid chromatography with electrospray ionization mass spectrometry. Following i.v. administration, clearance was 7.97±5.16 mL/kg/min, and half-life (T(1/2)) was 3.58 h (harmonic mean). Volume of distribution was 3.01±1.69 L/kg. Following i.m. administration, maximum concentration (C(max)) was 1.74±0.09 ng/mL, which was significantly lower than the highest measured concentration (4.34±1.22 ng/mL) after i.v. administration (P<0.001). Time to C(max) was 0.9±0.69 h and T(1/2) was 4.24 h. Bioavailability was variable (51-88%). Several horses showed signs of excitement. Gut sounds were decreased 10±2.19 and 8.67±1.63 h in the i.v. and i.m. group, respectively. Buprenorphine has a moderate T(1/2) in the horse and was detected at concentrations expected to be therapeutic in other species after i.v. and i.m. administration of 0.005 mg/kg. Signs of excitement and gastrointestinal stasis may be noted.}, number={1}, journal={Journal of Veterinary Pharmacology and Therapeutics}, author={Davis, J.L. and Messenger, K.M. and Lafevers, D.H. and Barlow, B.M. and Posner, L.P.}, year={2011}, month={Mar}, pages={52–58} }
 @article{wearn_crisman_davis_geor_hodgson_suagee_ashraf-khorassani_mccutcheon_2011, title={Pharmacokinetics of pioglitazone after multiple oral dose administration in horses}, volume={34}, ISSN={["0140-7783"]}, DOI={10.1111/j.1365-2885.2010.01217.x}, abstractNote={Pioglitazone is a thiazolidinedione class of antidiabetic agent with proven efficacy in increasing insulin sensitivity in humans with noninsulin-dependent diabetes mellitus, a syndrome of insulin resistance sharing similarities with equine metabolic syndrome. The purpose of this study was to determine the pharmacokinetics of pioglitazone in adult horses following multiple oral dose administration. Pioglitazone hydrochloride (1 mg/kg) was administered orally for 11 doses at 24-h intervals, and plasma samples were collected. Initially, a pilot study was performed using one horse; and thereafter the drug was administered to six horses. Samples were analyzed by liquid chromatography with tandem mass spectrometry, and pharmacokinetic parameters were calculated using noncompartmental modeling. The maximum plasma concentration was 509.1 ± 413.5 ng/mL achieved at 1.88 ± 1.39 h following oral administration of the first dose, and 448.1 ± 303.5 ng/mL achieved at 2.83 ± 1.81 h (mean ± SD) following the eleventh dose. Apparent elimination half-life was 9.94 ± 4.57 and 9.63 ± 5.33 h after the first and eleventh dose, respectively. This study showed that in healthy horses, pioglitazone administered at a daily oral dose of 1 mg/kg results in plasma concentrations and total drug exposure approximating, but slightly below, those considered therapeutic in humans.}, number={3}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Wearn, J. M. G. and Crisman, M. V. and Davis, J. L. and Geor, R. J. and Hodgson, D. R. and Suagee, J. K. and Ashraf-Khorassani, M. and McCutcheon, L. J.}, year={2011}, month={Jun}, pages={252–258} }
 @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} }
 @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={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 (t(1/2) k(10) ) of 12.49 ± 1.84 h. The average maximum plasma concentration (C(max) ) 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 IC(50) and IC(80) , respectively. Dosing simulations showed that concentrations above the IC(80) for COX-2 would be maintained following 2 mg/kg PO q12h, and above the IC(50) 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{clode_davis_salmon_lafevers_gilger_2010, title={Aqueous humor and plasma concentrations of ciprofloxacin and moxifloxacin following topical ocular administration in ophthalmologically normal horses}, volume={71}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.71.5.564}, DOI={10.2460/ajvr.71.5.564}, abstractNote={OBJECTIVE
To determine the degree of ocular penetration and systemic absorption of commercially available topical ophthalmic solutions of 0.3% ciprofloxacin and 0.5% moxifloxacin following repeated topical ocular administration in ophthalmologically normal horses.


ANIMALS
7 healthy adult horses with clinically normal eyes as evaluated prior to each treatment.


PROCEDURES
6 horses were used for assessment of each antimicrobial, and 1 eye of each horse was treated with topically administered 0.3% ciprofloxacin or 0.5% moxifloxacin (n = 6 eyes/drug) every 4 hours for 7 doses. Anterior chamber paracentesis was performed 1 hour after the final dose was administered, and blood samples were collected at 24 (immediately after the final dose), 24.25, 24.5, and 25 hours (time of aqueous humor [AH] collection). Plasma and AH concentrations of ciprofloxacin or moxifloxacin were determined by use of high-performance liquid chromatography.


RESULTS
Mean +/- SD AH concentrations of ciprofloxacin and moxifloxacin were 0.009 +/- 0.008 microg/mL and 0.071 +/- 0.029 microg/mL, respectively. The AH moxifloxacin concentrations were significantly greater than those of ciprofloxacin. Mean +/- SD plasma concentrations of ciprofloxacin were less than the lower limit of quantification. Moxifloxacin was detected in the plasma of all horses at all sample collection times, with a peak value of 0.015 microg/mL at 24 and 24.25 hours, decreasing to < 0.004 microg/mL at 25 hours.


CONCLUSIONS AND CLINICAL RELEVANCE
Moxifloxacin was better able to penetrate healthy equine corneas and reach measurable AH concentrations than was ciprofloxacin, suggesting moxifloxacin might be of greater value in the treatment of deep corneal or intraocular bacterial infections caused by susceptible organisms. Topical administration of moxifloxacin also resulted in detectable plasma concentrations.}, number={5}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Clode, Alison B. and Davis, Jennifer L. and Salmon, Jacklyn and LaFevers, Heath and Gilger, Brian C.}, year={2010}, month={May}, pages={564–569} }
 @article{sikorski_birkenheuer_holowaychuk_mccleary-wheeler_davis_littman_2010, title={Babesiosis Caused by a Large Babesia Species in 7 Immunocompromised Dogs}, volume={24}, ISSN={["1939-1676"]}, DOI={10.1111/j.1939-1676.2009.0440.x}, abstractNote={BACKGROUND
A large unnamed Babesia species was detected in a dog with lymphoma. It was unknown if this was an underrecognized pathogen.


OBJECTIVE
Report the historical and clinicopathologic findings in 7 dogs with babesiosis caused by a large unnamed Babesia species characterize the 18S ribosomal ribonucleic acid (rRNA) genes.


ANIMALS
Seven immunocompromised dogs from which the Babesia was isolated.


METHODS
Retrospective case review. Cases were identified by a diagnostic laboratory, the attending clinicians were contacted and the medical records were reviewed. The Babesia sp. 18S rRNA genes were amplified and sequenced.


RESULTS
Six of 7 dogs had been splenectomized; the remaining dog was receiving oncolytic drugs. Lethargy, anorexia, fever, and pigmenturia were reported in 6/7, 6/7, 4/7, and 3/7 dogs. Laboratory findings included mild anemia (7/7) and severe thrombocytopenia (6/7). Polymerase chain reaction (PCR) assays used to detect Babesia sensu stricto species were all positive, but specific PCR assays for Babesia canis and Babesia gibsoni were negative in all dogs. The 18S rRNA gene sequences were determined to be identical to a large unnamed Babesia sp. previously isolated. Cross-reactive antibodies against other Babesia spp. were not always detectable. Five dogs were treated with imidocarb dipropionate and 1 dog with atovaquone/azithromycin; some favorable responses were noted. The remaining dog was untreated and remained a clinically stable carrier.


CONCLUSIONS AND CLINICAL IMPORTANCE
Dogs with pigmenturia, anemia, and thrombocytopenia should be tested for Babesia sp. by PCR. Serology is not sufficient for diagnosis of this Babesia sp. Asplenia, chemotherapy, or both might represent risk factors for persistent infection, illness, or both.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Sikorski, L. E. and Birkenheuer, A. J. and Holowaychuk, M. K. and McCleary-Wheeler, A. L. and Davis, J. M. and Littman, M. P.}, year={2010}, pages={127–131} }
 @article{franje_chang_shyu_davis_lee_lee_chang_chou_2010, title={Differential heat stability of amphenicols characterized by structural degradation, mass spectrometry and antimicrobial activity}, volume={53}, ISSN={["1873-264X"]}, DOI={10.1016/j.jpba.2010.06.013}, abstractNote={Heat stability of amphenicols and the relationship between structural degradation and antimicrobial activity after heating has not been well investigated. Florfenicol (FF), thiamphenicol (TAP), and chloramphenicol (CAP) were heated at 100 °C in water, salt water, soybean sauce and chicken meat for up to 2 h. Degradation and antimicrobial activity of the compounds was evaluated using capillary electrophoresis (CE) with UV-DAD spectrometry, minimum inhibitory concentration (MIC) assay, and gas chromatography with electron impact ionization mass spectrometry (GC–EI-MS). Heat stability of amphenicols in matrices was ranked as water ≥ salt water > soybean sauce > meat, suggesting that heat degradation of amphenicols was accelerated in soybean sauce and was not protected in meat. Heat stability by drug and matrices was ranked as FF > TAP = CAP in water, FF = TAP > CAP in salt water, TAP ≥ FF = CAP in soybean sauce, and TAP ≥ FF = CAP in meat, indicating differential heat stability of amphenicols among the 3 drugs and in different matrices. In accordance with the less than 20% degradation, the MIC against Escherichia coli and Staphylococcus aureus did not change after 2 h heating in water. A 5-min heating of amphenicols in water by microwave oven generated comparable percentage degradation to boiling in water bath for 30 min to 1 h. Both CE and GC–MS analysis showed that heating of FF produced TAP but not FF amine as one of its breakdown products. In conclusion, despite close similarity in structure; amphenicols exhibited differential behavior toward heating degradation in solutions and protein matrices. Although higher degradations of amphenicols were observed in soybean sauce and meat, heating treatment may generate product with antimicrobial activity (FF to TAP), therefore, heating of amphenicol residues in food cannot always be assumed safe.}, number={4}, journal={JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS}, author={Franje, Catherine A. and Chang, Shao-Kuang and Shyu, Ching-Lin and Davis, Jennifer L. and Lee, Yan-Wen and Lee, Ren-Jye and Chang, Chao-Chin and Chou, Chi-Chung}, year={2010}, month={Dec}, pages={869–877} }
 @article{smith_davis_smith_gerard_campbell_foster_2010, title={Efficacy and Pharmacokinetics of Pantoprazole in Alpacas}, volume={24}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/j.1939-1676.2010.0508.x}, DOI={10.1111/j.1939-1676.2010.0508.x}, abstractNote={BACKGROUND
Despite frequent clinical use, information about the pharmacokinetics and efficacy of pantoprazole in camelids is not available.


OBJECTIVES
To examine the pharmacokinetics of both IV and SC pantoprazole and to determine whether pantoprazole administration would increase 3rd compartment pH in alpacas.


ANIMALS
Six healthy adult alpacas.


METHODS
Alpacas were fitted with a 3rd compartment cannula for measuring gastric pH. After recovery, alpacas received 1 mg/kg pantoprazole IV, q24h for 3 days or 2 mg/kg SC q24h for 3 days. Alpacas received both IV and SC pantoprazole, with a minimum of 3 weeks between treatments. Third compartment pH was recorded and plasma samples were taken for pharmacokinetic analysis.


RESULTS
Pantoprazole induced a slow but sustained increase in 3rd compartment pH when given by both the IV and SC routes. Third compartment pH was significantly increased as compared with baseline values (1.81+/-0.7; mean+/-SD) at 24 (2.47+/-0.8), 48 (3.53+/-1.0) and 72 hours (4.03+/-1.3) after daily IV administration of pantoprazole. Third compartment pH increased from 1.73+/-0.6 at baseline to 3.05+/-1.1, 4.02+/-1.4, and 3.61+/-1.6 at 24, 48, and 72 hours after SC administration, respectively. Pharmacokinetic analysis demonstrated that pantoprazole had a short elimination half-life (0.47+0.06 h) and a high clearance rate (12.2+/-2.9 mL/kg/min) after both IV and SC administration.


CONCLUSIONS AND CLINICAL RELEVANCE
Based on the results of this study, pantoprazole represents a safe and effective drug for increasing 3rd compartment pH in camelids. Either IV or SC administration is likely to be an effective treatment for gastric ulcers.}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Smith, G. W. and Davis, J. L. and Smith, S. M. and Gerard, M. P. and Campbell, N. B. and Foster, D. M.}, year={2010}, pages={949–955} }
 @article{chang_davis_cheng_shien_hsieh_koh_chou_2010, title={Pharmacokinetics and tissue depletion of florfenicol in Leghorn and Taiwan Native chickens}, volume={33}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2009.01155.x}, abstractNote={Florfenicol (Ff) is a synthetic antibiotic with a broad antibacterial spectrum and high therapeutic effectiveness that was specifically developed for veterinary use. In the present study, tissue residual levels and the pharmacokinetics of Ff after oral administration of 30 mg/kg to Leghorn and Taiwan Native chicken were studied. Furthermore, differential pharmacokinetics between leg and breast muscles were compared using samples collected from an optimized microdialysis model designed for avian species. Significant differences in C(max) were detected between the plasma and muscle microdialysates, and between the breast and leg microdialysates of the Leghorn chickens by noncompartmental pharmacokinetic analysis. After a single oral dose of Ff at 30 mg/kg, the drug was quickly absorbed and widely distributed with tissue penetration factors significantly different between leg and breast muscles. The serum protein binding of Ff was estimated to be 16.8 ± 1.2%. Significant breed differences in tissue depletion were noted and characterized by higher Ff concentration in the brain, lung, kidney and at least 12 h longer resident times in kidney, heart and spleen for Taiwan Native chicken. Results from this investigation demonstrate the practicality of using in vivo microdialysis in chickens for pharmacokinetic studies and reveal significant time-dependent differences in the free concentrations of Ff in leg and breast muscles. The tissue depletion study signified breed differences in tissue residue concentration and detection times between Leghorn and Taiwan Native chickens. Therefore, currently used withdrawal times for Ff in chickens can not be assumed safe for Taiwan Native chickens.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Chang, S. K. and Davis, J. L. and Cheng, C. N. and Shien, R. H. and Hsieh, M. K. and Koh, B. W. and Chou, C. C.}, year={2010}, month={Oct}, pages={471–479} }
 @article{davids_2010, title={Pharmacokinetics/pharmacodynamics of Quinapril in horses}, volume={30}, number={10}, journal={Journal of Equine Veterinary Science}, author={Davids, J.}, year={2010}, pages={537–537} }
 @article{cook_jones shults_mcdowell_campbell_davis_marshall_blikslager_2009, title={Anti-inflammatory effects of intravenously administered lidocaine hydrochloride on ischemia-injured jejunum in horses}, volume={70}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.70.10.1259}, DOI={10.2460/ajvr.70.10.1259}, abstractNote={OBJECTIVE
To investigate effects of lidocaine hydrochloride administered IV on mucosal inflammation in ischemia-injured jejunum of horses treated with flunixin meglumine.


ANIMALS
24 horses.


PROCEDURES
Horses received saline (0.9% NaCl) solution (SS; 1 mL/50 kg, IV [1 dose]), flunixin meglumine (1 mg/kg, IV, q 12 h), lidocaine (bolus [1.3 mg/kg] and constant rate infusion [0.05 mg/kg/min], IV, during and after recovery from surgery), or both flunixin and lidocaine (n = 6/group). During surgery, blood flow was occluded for 2 hours in 2 sections of jejunum in each horse. Uninjured and ischemia-injured jejunal specimens were collected after the ischemic period and after euthanasia 18 hours later for histologic assessment and determination of cyclooxygenase (COX) expression (via western blot procedures). Plasma samples collected prior to (baseline) and 8 hours after the ischemic period were analyzed for prostanoid concentrations.


RESULTS
Immediately after the ischemic period, COX-2 expression in horses treated with lidocaine alone was significantly less than expression in horses treated with SS or flunixin alone. Eighteen hours after the ischemic period, mucosal neutrophil counts in horses treated with flunixin alone were significantly higher than counts in other treatment groups. Compared with baseline plasma concentrations, postischemia prostaglandin E(2) metabolite and thromboxane B(2) concentrations increased in horses treated with SS and in horses treated with SS or lidocaine alone, respectively.


CONCLUSIONS AND CLINICAL RELEVANCE
In horses with ischemia-injured jejunum, lidocaine administered IV reduced plasma prostaglandin E(2) metabolite concentration and mucosal COX-2 expression. Coadministration of lidocaine with flunixin ameliorated the flunixin-induced increase in mucosal neutrophil counts.}, number={10}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Cook, Vanessa L. and Jones Shults, Jennifer and McDowell, Marsha R. and Campbell, Nigel B. and Davis, Jennifer L. and Marshall, John F. and Blikslager, Anthony T.}, year={2009}, month={Oct}, pages={1259–1268} }
 @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={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 degrees, 8 degrees, 25 degrees, or 37 degrees C without exposure to light or at 25 degrees 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 degrees C had undergone excessive degradation by day 14, samples stored at 37 degrees C had undergone excessive degradation by day 21, and samples stored at 25 degrees 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} }
 @article{smith_davis_baynes_yeatts_barlow_riviere_2009, title={Elimination kinetics of tilmicosin following intramammary administration in lactating dairy cattle}, volume={234}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.234.2.245}, DOI={10.2460/javma.234.2.245}, abstractNote={OBJECTIVE
To determine elimination kinetics of tilmicosin in milk following intramammary administration in lactating dairy cattle.


DESIGN
Prospective pharmacokinetic study.


ANIMALS
6 lactating dairy cows.


PROCEDURES
Following collection of baseline milk samples, 1,200 mg (4 mL) of tilmicosin was infused into the left front and right rear mammary glands of each cow. Approximately 12 hours later, an additional 1,200 mg of tilmicosin was infused into the left front and right rear glands after milking. Milk samples were then collected from each gland at milking time for 40 days. Concentration of tilmicosin was determined by means of ultraperformance liquid chromatography-mass spectrometry, and a milk withdrawal interval for tilmicosin was calculated on the basis of the tolerance limit method.


RESULTS
Although there was considerable variation between glands, concentration of tilmicosin was high in milk from treated glands and had a long half-life in treated and untreated glands. Tilmicosin was detected in all treated glands for the entire 40-day study period and was detected in untreated glands for approximately 30 to 35 days.


CONCLUSIONS AND CLINICAL RELEVANCE
Findings indicated that tilmicosin should not be administered by the intramammary route in lactating dairy cows. Milk from all glands of any cows accidentally treated should be discarded for a minimum of 82 days following intramammary administration.}, number={2}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Smith, Geof W. and Davis, Jennifer L. and Baynes, Ronald E. and Yeatts, James L. and Barlow, Beth M. and Riviere, Jim E.}, year={2009}, month={Jan}, pages={245–248} }
 @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} }
 @article{smith_gerard_campbell_foster_smith_davis_2009, title={Third-compartment cannulation in alpacas using a polyurethane gastrostomy tube}, volume={87}, ISSN={["1751-0813"]}, url={https://doi.org/10.1111/j.1751-0813.2009.00510.x}, DOI={10.1111/j.1751-0813.2009.00510.x}, abstractNote={OBJECTIVE
To develop a simple and effective surgical technique for third-compartment cannulation in alpacas.


DESIGN
Prospective study using six adult male alpacas.


METHODS
General anaesthesia was induced and a polyurethane gastrostomy tube was surgically implanted into the distal portion of the third compartment.


RESULTS
Three of the alpacas retained their cannulas for a 100-day period; however, three cannulas were dislodged during the study. Two of the three dislodged cannulas were replaced during a second surgical procedure. Cannulas were well tolerated by the alpacas and all animals remained clinically healthy during the study period. Third compartment contents did not leak from the cannulation site. The tubes were manually removed following the completion of the study and the small defect in the body wall quickly healed over in all animals.


CONCLUSION
Surgical placement of polyurethane tubes designed for percutaneous endoscopic gastrostomy is a useful method of cannulating the third compartment in camelids. This technique can be used for experimental studies and possibly could be used for nutritional support and fluid therapy in sick camelids that might need long-term care.}, number={12}, journal={AUSTRALIAN VETERINARY JOURNAL}, author={Smith, G. W. and Gerard, M. P. and Campbell, N. B. and Foster, D. M. and Smith, S. M. and Davis, J. L.}, year={2009}, month={Dec}, pages={487–491} }
 @article{davis_smith_baynes_tell_webb_riviere_2009, title={Update on drugs prohibited from extralabel use in food animals}, volume={235}, ISSN={["0003-1488"]}, DOI={10.2460/javma.235.5.528}, number={5}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Davis, Jennifer L. and Smith, Geof W. and Baynes, Ronald E. and Tell, Lisa A. and Webb, Alistair I. and Riviere, Jim E.}, year={2009}, month={Sep}, pages={528–534} }
 @article{cook_shults_mcdowell_campbell_davis_blikslager_2008, title={Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine}, volume={40}, DOI={10.2746/04251640SX293574}, number={4}, journal={Equine Veterinary Journal}, author={Cook, V. L. and Shults, J. J. and McDowell, M. and Campbell, N. B. and Davis, J. L. and Blikslager, Anthony}, year={2008}, pages={353–357} }
 @article{errico_trumble_bueno_davis_brown_2008, title={Comparison of two indirect techniques for local delivery of a high dose of an antimicrobial in the distal portion of forelimbs of horses}, volume={69}, ISSN={["0002-9645"]}, DOI={10.2460/ajvr.69.3.334}, abstractNote={Abstract}, number={3}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Errico, Jason A. and Trumble, Troy N. and Bueno, Aloisio C. D. and Davis, Jennifer L. and Brown, Murray P.}, year={2008}, month={Mar}, pages={334–342} }
 @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} }
 @article{smith_davis_tell_webb_riviere_2008, title={FARAD digest - Extralabel use of nonsteroidal anti-inflammatory drugs in cattle}, volume={232}, number={5}, journal={Journal of the American Veterinary Medical Association}, author={Smith, G. W. and Davis, J. L. and Tell, L. A. and Webb, A. I. and Riviere, J. E.}, year={2008}, pages={697–701} }
 @article{yi_davis_salmon_gilger_2008, title={Ocular distribution and toxicity of intravitreal injection of triamcinolone acetonide in normal equine eyes}, volume={11}, ISSN={1463-5216 1463-5224}, url={http://dx.doi.org/10.1111/j.1463-5224.2008.00636.x}, DOI={10.1111/j.1463-5224.2008.00636.x}, abstractNote={Abstract}, journal={Veterinary Ophthalmology}, publisher={Wiley}, author={Yi, N. Y. and Davis, J. L. and Salmon, J. H. and Gilger, B. C.}, year={2008}, month={Sep}, pages={15–19} }
 @article{douglas_yi_davis_salmon_gilger_2008, title={Ocular toxicity and distribution of subconjunctival and intravitreal rapamycin in horses}, volume={31}, ISSN={0140-7783 1365-2885}, url={http://dx.doi.org/10.1111/j.1365-2885.2008.00986.x}, DOI={10.1111/j.1365-2885.2008.00986.x}, abstractNote={ In vitro photosensitivity of rapamycin (RAPA) and ocular toxicity and distribution of intravitreal and subconjunctival RAPA was evaluated in normal horses. RAPA (2.5 mg, 5 mg, and 10 mg) was placed in 10 mL of PBS and maintained in a water bath at 37 °C, kept in the dark or subjected to room light, and sampled for up to 3 months for RAPA levels. Six normal adult horses received either 5 mg (n = 2) or 10 mg (n = 2) of RAPA intravitreally or 10 mg (n = 2) subconjunctivally. Ophthalmic exams and electroretinography (ERG) were performed prior to injection and on days 1, 7, 14, and 21 post‐injection. Eyes were enucleated and samples were collected for RAPA concentrations and histopathology. No difference in light vs. dark RAPA concentrations was observed, suggesting a lack of RAPA phototoxicity. No evidence of ocular toxicity was noted on ophthalmic examination or histopathology. RAPA was not detected intraocularly 7 days post‐injection in eyes receiving subconjunctival RAPA, but was detected in the vitreous at 21 days post‐injection. Drug could be detected in both the aqueous and vitreous humor after intravitreal injection. Further study is needed to determine the efficacy of intravitreal RAPA.}, number={6}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Douglas, L. C. and Yi, N. Y. and Davis, J. L. and Salmon, J. H. and Gilger, B. C.}, year={2008}, month={Dec}, pages={511–516} }
 @article{flammer_nettifee osborne_webb_foster_dillard_davis_2008, title={Pharmacokinetics of voriconazole after oral administration of single and multiple doses in African grey parrots (Psittacus erithacus timneh)}, volume={69}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.69.1.114}, DOI={10.2460/ajvr.69.1.114}, abstractNote={Abstract}, number={1}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Flammer, Keven and Nettifee Osborne, Julie A. and Webb, Donna J. and Foster, Laura E. and Dillard, Stacy L. and Davis, Jennifer L.}, year={2008}, month={Jan}, pages={114–121} }
 @article{davis_2008, title={The use of antifungals}, volume={29}, number={7}, journal={Veterinary Technician}, author={Davis, J. L.}, year={2008}, pages={428-} }
 @article{little_brown_campbell_moeser_davis_blikslager_2007, title={Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum}, volume={68}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.68.6.614}, DOI={10.2460/ajvr.68.6.614}, abstractNote={Abstract}, number={6}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Little, Dianne and Brown, S. Aubrey and Campbell, Nigel B. and Moeser, Adam J. and Davis, Jennifer L. and Blikslager, Anthony T.}, year={2007}, month={Jun}, pages={614–624} }
 @article{davis_posner_elce_2007, title={Gabapentin for the treatment of neuropathic pain in a pregnant horse}, volume={231}, ISSN={["1943-569X"]}, DOI={10.2460/javma.231.5.755}, abstractNote={Abstract}, number={5}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Davis, Jennifer L. and Posner, Lysa P. and Elce, Yvonne}, year={2007}, month={Sep}, pages={755–758} }
 @article{morton_davis_redding_jones_2007, title={Nonsecretory multiple myeloma in a horse}, volume={19}, ISSN={["0957-7734"]}, DOI={10.2746/095777307X217852}, abstractNote={Equine Veterinary EducationVolume 19, Issue 11 p. 564-568 Nonsecretory multiple myeloma in a horse A. J. Morton, Corresponding Author A. J. Morton University of Florida Veterinary Medical Center, Department of Large Animal Clinical Sciences, Box 100136 Gainesville, Florida 32610, USA*University of Florida Veterinary Medical Center, Department of Large Animal Clinical Sciences, Box 100136 Gainesville, Florida 32610, USASearch for more papers by this authorJ. L. Davi, J. L. Davi North Carolina State University Veterinary Medical Teaching Hospital, Department of Clinical Sciences, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorW. R. Redding, W. R. Redding North Carolina State University Veterinary Medical Teaching Hospital, Department of Clinical Sciences, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorS. L. Jones, S. L. Jones North Carolina State University Veterinary Medical Teaching Hospital, Department of Clinical Sciences, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this author A. J. Morton, Corresponding Author A. J. Morton University of Florida Veterinary Medical Center, Department of Large Animal Clinical Sciences, Box 100136 Gainesville, Florida 32610, USA*University of Florida Veterinary Medical Center, Department of Large Animal Clinical Sciences, Box 100136 Gainesville, Florida 32610, USASearch for more papers by this authorJ. L. Davi, J. L. Davi North Carolina State University Veterinary Medical Teaching Hospital, Department of Clinical Sciences, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorW. R. Redding, W. R. Redding North Carolina State University Veterinary Medical Teaching Hospital, Department of Clinical Sciences, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this authorS. L. Jones, S. L. Jones North Carolina State University Veterinary Medical Teaching Hospital, Department of Clinical Sciences, 4700 Hillsborough Street, Raleigh, North Carolina 27606, USASearch for more papers by this author First published: 05 January 2010 https://doi.org/10.2746/095777307X217852Citations: 5AboutPDF ToolsExport 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 Volume19, Issue11December 2007Pages 564-568 RelatedInformation}, number={11}, journal={EQUINE VETERINARY EDUCATION}, author={Morton, A. J. and Davis, J. L. and Redding, W. R. and Jones, S. L.}, year={2007}, month={Dec}, pages={564–568} }
 @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{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{clode_davis_salmon_michau_gilger_2006, title={Evaluation of concentration of voriconazole in aqueous humor after topical and oral administration in horses}, volume={67}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.67.2.296}, DOI={10.2460/ajvr.67.2.296}, abstractNote={Abstract}, number={2}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Clode, Alison B. and Davis, Jennifer L. and Salmon, Jacklyn and Michau, Tammy Miller and Gilger, Brian C.}, year={2006}, month={Feb}, pages={296–301} }
 @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}, 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{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}, 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{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} }
 @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={Abstract}, 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{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{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{davis_gilger_robinson_2004, title={Novel approaches to ocular drug delivery}, volume={6}, number={2}, journal={Current Opinion in Molecular Therapeutics}, author={Davis, J. L. and Gilger, B. C. and Robinson, M. R.}, year={2004}, pages={195–205} }
 @article{bertoni_duren-winfield_ambrosius_mcardle_sueta_massing_peacock_davis_croft_goff_2004, title={Quality of heart failure care in managed Medicare and Medicaid patients in North Carolina}, volume={93}, ISSN={0002-9149}, url={http://dx.doi.org/10.1016/j.amjcard.2003.11.053}, DOI={10.1016/j.amjcard.2003.11.053}, abstractNote={<h2>Abstract</h2> Use of angiotensin-converting enzyme (ACE) inhibitors and β-adrenergic receptor blockers in patients with heart failure (HF) remains low despite the results of clinical trials and evidence-based guidelines that support their use. The quality of HF care in managed Medicare and Medicaid programs in North Carolina participating in a HF quality improvement program was assessed. Managed care plans identified adult patients with 1 inpatient or 3 outpatient claims for HF during 2000. A stratified random sample of 971 Medicare and 642 Medicaid patients' outpatient medical records from 5 plans were reviewed by trained nurse abstractors to obtain data regarding type of HF, demographics, comorbidities, and therapies. Left ventricular function assessment was performed in 88% of patients. Among 494 patients with systolic dysfunction, 86% were appropriately treated with respect to ACE inhibitors (73% prescribed, 13% had a documented contraindication). In contrast, β-blocker therapy was appropriate in 61% (49% prescribed, 12% contraindication). There were no significant differences in drug use by insurance, gender, race, or age. Ventricular function assessment and ACE inhibitor prescription rates are higher than β-blocker prescription rates among Medicare and Medicaid managed care patients in North Carolina. Opportunities for improvement remain, particularly for β-blocker use.}, number={6}, journal={The American Journal of Cardiology}, publisher={Elsevier BV}, author={Bertoni, Alain G and Duren-Winfield, Vanessa and Ambrosius, Walter T and McArdle, Jill and Sueta, Carla A and Massing, Mark W and Peacock, Sharon and Davis, Jennifer and Croft, Janet B and Goff, David C, Jr}, year={2004}, month={Mar}, pages={714–718} }
 @article{davis_blikslager_catto_jones_2003, title={A retrospective analysis of hepatic injury in horses with proximal enteritis (1984-2002)}, volume={17}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2003)017<0896:ARAOHI>2.3.CO;2}, number={6}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Davis, JL and Blikslager, AT and Catto, K and Jones, SL}, year={2003}, pages={896–901} }
 @article{davis_jones_2003, title={Equine primary immunodeficiencies}, volume={25}, number={7}, journal={Compendium on Continuing Education for the Practicing Veterinarian}, author={Davis, J. L. and Jones, S. L.}, year={2003}, pages={548–556} }
 @article{davis_jones_2003, title={Suppurative cholangiohepatitis and enteritis in adult horses}, volume={17}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2003)017<0583:SCAEIA>2.3.CO;2}, abstractNote={Journal of Veterinary Internal MedicineVolume 17, Issue 4 p. 583-587 Open Access Suppurative Cholangiohepatitis and Enteritis in Adult Horses Jennifer L. Davis, Jennifer L. Davis Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorSamuel L. Jones, Samuel L. Jones Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC DVM, PhD, DACVIM, College of Veterinary Medicine, North Carolina State University, 4700Hillsborough Street, Raleigh, NC 27606; E-mail: [email protected]Search for more papers by this author Jennifer L. Davis, Jennifer L. Davis Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NCSearch for more papers by this authorSamuel L. Jones, Samuel L. Jones Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC DVM, PhD, DACVIM, College of Veterinary Medicine, North Carolina State University, 4700Hillsborough Street, Raleigh, NC 27606; E-mail: [email protected]Search for more papers by this author First published: 28 June 2008 https://doi.org/10.1111/j.1939-1676.2003.tb02483.xCitations: 13 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 References 1 Thornburg LP, Kintner LD. Cholangiohepatitis in a horse. Vet Med Small Anim Clin 1980; 75: 1895– 1896. 2 Johnston JK, Divers TJ, Reef VB, et al. Cholelithiasis in horses: Ten cases (1982–1986). J Am Vet Med Assoc 1989; 194: 405– 409. 3 Peek SF, Divers TJ. Medical treatment of cholangiohepatitis and cholelithiasis in mature horses: 9 cases (1991–1998). Equine Vet J 2000; 32: 301– 306. 4 Pearson EG. Liver disease in the mature horse. Equine Vet Educ 1999; 11: 87– 96. 5 Gerros TC. Gallbladder and biliary tract disease. In: BP Smith, ed. Large Animal Internal Medicine, 2nd ed. St Louis , MO : Mosby; 1996: 946– 948. 6 Acland HM, Gunson DE, Gillette DM. Ulcerative duodenitis in foals. Vet Pathol 1983; 20: 653– 661. 7 Ettlinger JJ, Ford T., Palmer JE. Ulcerative duodenitis with lu-minal constriction in two horses. J Am Vet Med Assoc 1990; 196: 1628– 1630. 8 Zeuzem S.. Gut-liver axis. Int J Colorectal Dis 2000; 15: 59– 82. 9 Schulz KS, Simmons TR, Johnson R.. Primary cholangiohepatitis in a horse. Cornell Vet 1990; 80: 35– 40. 10 Crawford JM. Biliary system. In: SL Robbins, ed. Pathologic Basis of Disease, 5th ed. Philadelphia , PA : WB Saunders; 1994: 883– 896. 11 Hanau LH, Steigbigel NH. Acute (ascending) cholangitis. Infect Dis Clin North Am 2000; 14: 521– 546. 12 Madara JL. Pathobiology of the intestinal epithelial barrier. Am J Pathol 1990; 137: 1273– 1281. 13 Losser M., Payen D.. Mechanisms of liver damage. Semin Liver Dis 1996; 16: 357– 367. 14 Tennant B.. Acute hepatitis in horses: Problems of differentiating toxic and infectious causes in the adult. Proceedings of the 24th Annual Convention of the American Association of Equine Practitioners, St. Louis, MO, 1978. 15 Al-Mashat RR, Taylor DJ. Bacteria in enteric lesions of horses. Vet Rec 1986; 118: 453– 458. 16 Matthews S., Dart AJ, Dowling BA, et al. Peritonitis associated with Actinobacillus equuli in horses: 51 cases. Aust Vet J 2001; 79: 536– 539. 17 Seahorn TL, Cornick JL, Cohen ND. Prognostic indicators for horses with duodenitis-proximal jejunitis. J Vet Int Med 1992; 6: 307– 311. 18 Johnston JK, Morris DD. Comparison of duodenitis/proximal jejunitis and small intestinal obstruction in horses: 68 cases (1977-- 1985). J Am Vet Med Assoc 1987; 191: 849– 854. Citing Literature Volume17, Issue4July 2003Pages 583-587 ReferencesRelatedInformation}, number={4}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Davis, JL and Jones, SL}, year={2003}, pages={583–587} }
 @article{davis_stewart_brazik_gilger_2003, title={The effect of topical administration of atropine sulfate on the normal equine pupil: influence of age, breed and gender}, volume={6}, ISSN={["1463-5224"]}, DOI={10.1111/j.1463-5224.2003.00315.x}, abstractNote={Abstract}, number={4}, journal={VETERINARY OPHTHALMOLOGY}, author={Davis, JL and Stewart, T and Brazik, E and Gilger, BC}, year={2003}, month={Dec}, pages={329–332} }
 @article{davis_2003, title={Treatment of peritonitis}, volume={19}, ISSN={["0749-0739"]}, DOI={10.1016/j.cveq.2003.08.007}, abstractNote={In summary, peritonitis in the horse is a potentially life-threatening disease that must be treated promptly and aggressively. Therapy should be aimed at reducing systemic shock and hypovolemia, correction of the primary cause, antibiotic and anti-inflammatory therapy, and abdominal drainage and lavage. The prognosis depends on the ability to diagnose and treat the underlying cause and prevent the development of complications. Mortality rates can be as high as 59.7%, with horses developing postoperative peritonitis having a 56% mortality rate. Long-term complications like adhesion formation or internal abscesses may further reduce the survival rate. The prognosis is best determined by an early and quick response to aggressive treatment.}, number={3}, journal={VETERINARY CLINICS OF NORTH AMERICA-EQUINE PRACTICE}, author={Davis, JL}, year={2003}, month={Dec}, pages={765-+} }
 @article{davis_gardner_schwabenton_breuhaus_2002, title={Congestive heart failure in horses: 14 cases (1984-2001)}, volume={220}, ISSN={["0003-1488"]}, DOI={10.2460/javma.2002.220.1512}, abstractNote={Abstract}, number={10}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Davis, JL and Gardner, SY and Schwabenton, B and Breuhaus, BA}, year={2002}, month={May}, pages={1512–1515} }
 @article{davis_gilger_spaulding_robertson_jones_2002, title={Nasal adenocarcinoma with diffuse metastases involving the orbit, cerebrum, and multiple cranial nerves in a horse}, volume={221}, ISSN={["0003-1488"]}, url={http://europepmc.org/abstract/med/12458617}, DOI={10.2460/javma.2002.221.1460}, abstractNote={A 9-year-old Trakehner gelding was examined because of right exophthalmus. Clinical findings included a lack of menace response in the right eye, reduced direct and consensual right pupillary light reflexes, ventrolateral strabismus of the right eye, mild right-sided facial asymmetry, a head tilt to the left, and increased extensor tone in the right limbs. Findings were suggestive of a multifocal lesion affecting the right forebrain; right optic, oculomotor, and facial nerves; and left vestibulocochlear nerve. Ultrasonographic examination of the right eye revealed a vascular retrobulbar mass. Computed tomographic imaging revealed a mass that filled the nasal cavity and invaded the forebrain. Necropsy revealed an undifferentiated nasal adenocarcinoma affecting the orbit with metastases to the right parotid gland, cranial cervical lymph nodes, fascial planes of the neck, and lungs. No evidence of direct involvement of the right facial and left vestibulocochlear nerves was found, suggesting the possibility of paraneoplastic peripheral neuropathy.}, number={10}, journal={JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Davis, JL and Gilger, BC and Spaulding, K and Robertson, ID and Jones, SL}, year={2002}, month={Nov}, pages={1460–1463} }
 @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{davis_ramirez_campbell_jones_2001, title={Acute and chronic mineral oil pneumonitis in two horses}, volume={13}, DOI={10.1111/j.2042-3292.2001.tb00099.x}, abstractNote={Equine Veterinary EducationVolume 13, Issue 5 p. 230-234 Acute and chronic mineral oil pneumonitis in two horses J. L. Davis, J. L. Davis Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.Search for more papers by this authorS. Ramirez, S. Ramirez Anatomy, Physiology and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.Search for more papers by this authorN. Campbell, N. Campbell Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.Search for more papers by this authorS. L. Jones, Corresponding Author S. L. Jones Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.†Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.Search for more papers by this author J. L. Davis, J. L. Davis Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.Search for more papers by this authorS. Ramirez, S. Ramirez Anatomy, Physiology and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.Search for more papers by this authorN. Campbell, N. Campbell Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.Search for more papers by this authorS. L. Jones, Corresponding Author S. L. Jones Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.†Departments of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, USA.Search for more papers by this author First published: 05 January 2010 https://doi.org/10.1111/j.2042-3292.2001.tb00099.xCitations: 6AboutPDF ToolsExport 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 Blinkhorn, R.J. (1998) Embolic infections of the lung and lipoid pneumonia. In: Textbook of Pulmonary Diseases, Vol. I, 6th edn., Eds: G.L. Baum, J.D. Crapo, B.R. Celli and J.B. Karlinsky, Lippincott-Raven, Philadelphia. pp 639–644. Google Scholar Cassiere, H.A. and Niederman, M.S. (1998) Aspiration pneumonia, lipoid pneumonia and lung abscesses. In: Textbook of Pulmonary Diseases, Vol. I, 6th edn., Eds: G.L. Baum, J.D. Crapo, B.R. Celli and J.B. Karlinsky, Lippincott-Raven, Philadelphia. pp 645–654. Google Scholar Corcoran, B.M., Martin, M., Danke, P.G.G., Anderson, A., Head, K.W., Clutton, R.E., Else, R.W. and Fuentes, V.L. (1992) Lipoid pneumonia in a rough collie dog. J. small Anim. Pract. 33, 544–548. 10.1111/j.1748-5827.1992.tb01050.x Web of Science®Google Scholar Scarratt, W.K., Moon, M.L., Sponenberg, D.P. and Feldman, B. (1998) Inappropriate administration of mineral oil resulting in lipoid pneumonia in three horses. Equine vet. J. 30, 85–88. 10.1111/j.2042-3306.1998.tb04094.x CASPubMedWeb of Science®Google Scholar Stauffer, B.D. (1982) Stomach intubation accidents. J. Am. vet. med. Ass. 181, 448. CASPubMedWeb of Science®Google Scholar Sweeney, C.R. and Baker, J.C. (1996) Diseases of the respiratory system. In: Large Animal Internal Medicine, 2nd edn., Ed: B.P. Smith, Mosby, St. Louis. pp 650–651. Google Scholar Wright, J.L. (1995) Consequences of aspiration and bronchial obstruction. In: Pathology of the Lung, 2nd edn., Ed: W.M. Thurlbeck and A.M. Churg, Thieme Medical Publishing, New York. pp 1111–1129. Google Scholar Citing Literature Volume13, Issue5October 2001Pages 230-234 ReferencesRelatedInformation}, number={5}, journal={Equine Veterinary Education}, author={Davis, J. L. and Ramirez, S. and Campbell, N. and jones}, year={2001}, pages={230–234} }
 @misc{baynes_dedonder_kissell_mzyk_marmulak_smith_tell_gehring_davis_riviere, title={Health concerns and management of select veterinary drug residues}, volume={88}, journal={Food and Chemical Toxicology}, author={Baynes, R. E. and Dedonder, K. and Kissell, L. and Mzyk, D. and Marmulak, T. and Smith, G. and Tell, L. and Gehring, R. and Davis, J. and Riviere, J. E.}, pages={112–122} }