@article{wimbish_lynch_knych_ueda_messenger_2024, title={Pharmacokinetics of a continuous intravenous infusion of hydromorphone in healthy dogs}, volume={11}, ISSN={["2297-1769"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85191704117&partnerID=MN8TOARS}, DOI={10.3389/fvets.2024.1362730}, abstractNote={Introduction Dosing recommendations for hydromorphone intravenous constant rate infusion (IV CRI) are derived from simulations following IV bolus administration. While this extrapolated dose regimen has been described clinically, pharmacokinetics (PK) of hydromorphone infusions in dogs are not yet described. The study objective was to describe the PK of hydromorphone in healthy dogs receiving an IV bolus followed by an IV CRI for 48 h. Methods A prospective, experimental study was performed involving the administration of hydromorphone (0.1 mg/kg IV bolus then IV CRI 0.01 mg/kg/h over a 48 h period) to 6 healthy Beagle dogs. Blood samples were collected at 16 time points between 0 and 58 h relative to the initial bolus. Plasma hydromorphone concentrations were analyzed by high pressure liquid chromatography with tandem mass spectrometry detection. Pharmacokinetic parameter estimates were obtained with compartmental methods using commercially available software. Results A two-compartment model with first order elimination was used. At the end of the infusion, median (range) plasma hydromorphone concentrations were 6.8 (5.5–19.6) ng/mL. The median total body clearance was 30.4 (19.8–36.7) mL/min/kg; volume of distribution at steady state was 4.5 (3.2–7.8) L/kg; and terminal elimination half-life was 11.2 (7.6–24.3) h. Conclusion Hydromorphone (0.1 mg/kg IV bolus then IV CRI of 0.01 mg/kg/h) maintained steady-state plasma concentrations above the minimum human analgesic target in healthy Beagle dogs with minimal side effects. Further studies are needed to determine the effective plasma concentrations of hydromorphone in painful dogs.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Wimbish, Candace and Lynch, Alex M. and Knych, Heather K. and Ueda, Yu and Messenger, Kristen M.}, year={2024}, month={Apr} }
 @article{wiloch_enomoto_smith_baynes_messenger_2024, title={Pharmacokinetics of intranasal and intramuscular flunixin in healthy grower pigs}, volume={1}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/jvp.13426}, DOI={10.1111/jvp.13426}, abstractNote={Flunixin meglumine is a nonsteroidal anti-inflammatory drug approved to manage pyrexia associated with swine respiratory disease. In the United States, no analgesic drugs are approved for use in swine by the FDA, although they are needed to manage painful conditions. This study evaluated the pharmacokinetics and relative bioavailability of intranasal versus intramuscular flunixin in grower pigs. Six pigs received 2.2 mg/kg flunixin either intranasally via atomizer or intramuscularly before receiving flunixin via the opposite route following a 5-day washout period. Plasma samples were collected over 60 h and analysed using ultra-performance liquid chromatography and tandem mass spectrometry to detect flunixin plasma concentrations. A non-compartmental pharmacokinetic analysis was performed. The median C}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Wiloch, Emily E. and Enomoto, Hiroko and Smith, Lilly and Baynes, Ronald E. and Messenger, Kristen M.}, year={2024}, month={Jan} }
 @article{colon_early_munana_olby_mariani_mancini_fefer_li_briley_bailey_et al._2024, title={Pharmacokinetics of subcutaneous ketamine administration via the Omnipod® system in dogs}, volume={3}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.13440}, abstractNote={Abstract Ketamine is an injectable anesthetic agent with analgesic and antidepressant effects that can prevent maladaptive pain. Ketamine is metabolized by the liver into norketamine, an active metabolite. Prior rodent studies have suggested that norketamine is thought to contribute up to 30% of ketamine's analgesic effect. Ketamine is usually administered as an intravenous (IV) bolus injection or continuous rate infusion (CRI) but can be administered subcutaneously (SC) and intramuscularly (IM). The Omnipod® is a wireless, subcutaneous insulin delivery device that adheres to the skin and delivers insulin as an SC CRI. The Omnipod® was used in dogs for postoperative administration of ketamine as a 1 mg/kg infusion bolus (IB) over 1 hour (h). Pharmacokinetics (PK) showed plasma ketamine concentrations between 42 and 326.1 ng/mL. The median peak plasma concentration was 79.5 (41.9–326.1) ng/mL with a Tmax of 60 (30–75) min. After the same infusion bolus, the corresponding norketamine PK showed plasma drug concentrations between 22.0 and 64.8 ng/mL. The median peak plasma concentration was 43.0 (26.1–71.8) ng/mL with a median Tmax of 75 min. The median peak ketamine plasma concentration exceeded 100 ng/mL in dogs for less than 1 h post infusion. The Omnipod® system successfully delivered subcutaneous ketamine to dogs in the postoperatively.}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Colon, Claudia and Early, Peter and Munana, Karen and Olby, Natasha and Mariani, Christopher and Mancini, Shelby and Fefer, Gilad and Li, Zhong and Briley, Jessica and Bailey, Kate and et al.}, year={2024}, month={Mar} }
 @article{merenda_lopez-soriano_anderson_trindade_tomacheuski_leidig_messenger_ferreira_pairis-garcia_2024, title={Prostaglandin E<sub>2</sub> is an unreliable biomarker for inflammation in castrated piglets: a randomized controlled trial assessing pharmaceutical drug efficiency}, volume={85}, ISSN={["1943-5681"]}, url={http://dx.doi.org/10.2460/ajvr.24.04.0096}, DOI={10.2460/ajvr.24.04.0096}, abstractNote={To investigate the effect of intranasal (IN) flunixin meglumine (FM) and intra-inguinal (IG) lidocaine on castration inflammation using prostaglandin E2 (PGE2) concentration as a biomarker.}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Merenda, Victoria R. and Lopez-Soriano, Magdiel and Anderson, Stephanie and Trindade, Pedro H. E. and Tomacheuski, Rubia M. and Leidig, Martin S. and Messenger, Kristen and Ferreira, Juliana B. and Pairis-Garcia, Monique D.}, year={2024}, month={Oct} }
 @article{salmon_coleman_lynn_sanders_messenger_2024, title={Single- and multiple-dose pharmacokinetics of sotalol hydrochloride in healthy cats}, volume={51}, ISSN={["1875-0834"]}, DOI={10.1016/j.jvc.2023.11.015}, abstractNote={To describe the single- and multiple-dose pharmacokinetics and urinary elimination of sotalol in healthy cats. Six adult purpose-bred cats. Cats were administered 2 mg sotalol/kg body weight as a single intravenous bolus and as a single oral dose in a randomized crossover study with a 2-week washout period. The same cats then received 3 mg sotalol/kg orally every 12 hours for 2 weeks. Blood samples were collected at pre-determined time points for 48 hours post-dose for quantification of sotalol using ultra-high-pressure liquid chromatography with mass spectrometry. Non-compartmental analysis was used to obtain pharmacokinetic parameters. Data are presented as median (min-max). Following intravenous administration, plasma clearance and volume of distribution were 9.22 mL/min/kg (5.69-10.89) and 2175.56 (1961-2341.57) mL/kg, respectively. Bioavailability was 88.41% (62.75-130.29) following a single oral dose. Peak plasma concentration (Cmax) and time to Cmax were 0.94 μg/mL (0.45-1.17) and 1.5 h (0.5-4) after a single oral dose (2 mg/kg), and 2.29 μg/mL (1.91-2.48) and 1.0 h (0.5-1.5) with chronic oral dosing (3 mg/kg). Elimination half-life was 2.75 hours (2.52-4.10) and 4.29 hours (3.33-5.53) for single and chronic oral dosing, respectively. Accumulation index was 1.17 (1.09-1.29) after chronic dosing. Urinary sotalol recovery was 81-108% of the intravenous dose. Oral sotalol administration resulted in plasma concentrations reportedly efficacious in other species, with good-to-excellent oral bioavailability. Urinary excretion appears to be a major route of elimination. Following repeated oral dosing, minimal drug accumulation was estimated. Additional studies in cats are recommended due to the possibility of nonlinear kinetics.}, journal={JOURNAL OF VETERINARY CARDIOLOGY}, author={Salmon, S. J. and Coleman, A. E. and Lynn, C. R. and Sanders, J. E. and Messenger, K. M.}, year={2024}, month={Feb}, pages={86–96} }
 @article{hallowell_dembek_horne_knych_messenger_schnabel_2024, title={Systemic absorption of triamcinolone acetonide is increased from intrasynovial versus extrasynovial sites and induces hyperglycemia, hyperinsulinemia, and suppression of the hypothalamic-pituitary-adrenal axis}, volume={11}, ISSN={2297-1769}, url={http://dx.doi.org/10.3389/fvets.2024.1388470}, DOI={10.3389/fvets.2024.1388470}, abstractNote={Steroid-associated laminitis remains a major concern with use of corticosteroids in horses. Individual case factors such as joint pathology, pre-existing endocrinopathies, or corticosteroid type, dose, and timing influencing steroid-induced laminitis risk have not been investigated. This study aimed to determine if systemic absorption of triamcinolone acetonide (TA) varies between intrasynovial (antebrachiocarpal) and extrasynovial (sacroiliac) injection sites, and to determine the effects of TA absorption on glucose, insulin, cortisol, and adrenocorticotropic hormone (ACTH). Twenty adult horses were randomized into antebrachiocarpal or sacroiliac joint injection groups, and each horse received bilateral injections with a total dose of 18 mg triamcinolone. Blood was collected prior to injection and at 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 36, 48, 60, and 72 h post-injection. Peak TA absorption occurred at 8 h in both groups, and was significantly higher in the intrasynovial group compared to the extrasynovial group (1.397 ng/mL, 0.672 ng/mL,}, journal={Frontiers in Veterinary Science}, publisher={Frontiers Media SA}, author={Hallowell, Kimberly L. and Dembek, Katarzyna and Horne, Caitlyn R. and Knych, Heather K. and Messenger, Kristen M. and Schnabel, Lauren V.}, year={2024}, month={May} }
 @article{wallace_love_gensler_jacob_robertson_messenger_2023, title={Comparative growth dynamics of bacterial and fungal contaminants in bupivacaine liposomal injectable suspension, bupivacaine 0.5%, and propofol}, volume={18}, ISSN={["1932-6203"]}, url={http://europepmc.org/abstract/med/36795683}, DOI={10.1371/journal.pone.0281768}, abstractNote={Objective To determine whether bupivacaine liposomal injectable suspension (BLIS) supports microbial growth when artificially inoculated and to evaluate liposomal stability in the face of this extrinsic contamination as evidenced by changes in free bupivacaine concentrations. Study design A randomized, prospective in vitro study in which three vials of each BLIS, bupivacaine 0.5%, and propofol were individually inoculated with known concentrations of Escherichia coli , Pseudomonas aeruginosa , Staphylococcus aureus , and Candida albicans (n = 36) to quantify bacterial and fungal growth was conducted. Over 120 hours, aliquots from contaminated vials were withdrawn, plated, and incubated to determine microbial concentrations. High-pressure liquid chromatography (HPLC) was used to evaluate free bupivacaine concentrations over time in BLIS. Data were analyzed using a mixed effects model with multiple comparisons. Sample population Twelve vials of each BLIS, bupivacaine 0.5%, and propofol. Results BLIS did not support significant growth of Staphylococcus aureus or Candida albicans at any time. BLIS supported significant growth of Escherichia coli and Pseudomonas aeruginosa beginning at the 24 hour time point. Bupivacaine 0.5% did not support significant growth of any organisms. Propofol supported significant growth of all organisms. Free bupivacaine concentrations changed minimally over time. Conclusion Bacterial and fungal contaminant growth in artificially inoculated BLIS is organism dependent. BLIS supports significant growth of Escherichia coli and Pseudomonas aeruginosa . Extra-label handling of BLIS should only be undertaken with caution and with adherence to strict aseptic technique.}, number={2}, journal={PLOS ONE}, author={Wallace, Amber and Love, Lydia and Gensler, Catherine and Jacob, Megan and Robertson, James and Messenger, Kristen}, editor={Nevárez-Moorillón, Guadalupe VirginiaEditor}, year={2023}, month={Feb} }
 @article{lopez-soriano_merenda_anderson_trindade_leidig_messenger_ferreira_pairis-garcia_2023, title={Efficacy of inguinal buffered lidocaine and intranasal flunixin meglumine on mitigating physiological and behavioral responses to pain in castrated piglets}, volume={4}, ISSN={["2673-561X"]}, url={http://dx.doi.org/10.3389/fpain.2023.1156873}, DOI={10.3389/fpain.2023.1156873}, abstractNote={Managing castration pain on US sow farms is hindered by the lack of Food and Drug Administration (FDA) approved products for mitigating pain. Previous work assessing flunixin meglumine (FM) efficacy in mitigating castration pain has shown the drug to be effective in pigs, meanwhile, results from previous work evaluating lidocaine efficacy are contradictory. Therefore, the objectives of this study were to determine the efficacy of inguinal buffered lidocaine (BL) and FM in mitigating castration pain in piglets. This study was divided into Part I (physiological response) and Part II (behavioral response). For part I piglets were randomly assigned to the following treatments: T1: (C) Castration plus physiological saline; T2: (S) Sham plus physiological saline; T3: (CL) Castration plus BL; T4: (SL) Sham plus BL; T5: (CF) Castration plus FM; T6: (SF) Sham plus FM; T7: (CLF) Castration plus BL and FM; T8: (SLF) Sham plus BL and FM. Blood was collected 24 h prior to castration, 1 h, and 24 h post castration for cortisol quantification. For Part II another cohort of piglets was enrolled and randomly assign to the following treatments: T1: (C) Castration plus physiological saline and T7: (CLF) Castration plus BL and FM. Behavior scoring was obtained in real-time by observing each piglet for 4-min continuously using Unesp-Botucatu pig acute pain scale (UPAPS) at the following timepoints: 1 h before castration (-1 h), immediately post-castration (0 h), and 3 h post-castration (+3 h). Average cortisol concentrations did not differ at -24 h (P > 0.05) or at 24 h post-castration (P > 0.05) between treatments. At 1 h post-castration, castrated piglets (C and CL) demonstrated greater cortisol concentrations (P < 0.05). Castrated piglets in the CF and CLF group had lower cortisol concentrations compared to C and CL-treated pigs (P < 0.05). For behavioral response, there were no differences between treatments on total UPAPS scores (C and CLF, P > 0.05). Intranasal FM was able to effectively reduce the physiological piglet's response immediately post-castration. Inguinal buffered lidocaine had no effect on the either physiological or behavioral response to pain. Long-term research should focus on refining injection techniques for inguinal BL and consider administration frequency and dosing of intranasal FM to control pain for a longer period post-castration.}, journal={FRONTIERS IN PAIN RESEARCH}, publisher={Frontiers Media SA}, author={Lopez-Soriano, Magdiel and Merenda, Victoria Rocha and Anderson, Stephanie and Trindade, Pedro Henrique Esteves and Leidig, Martin S. and Messenger, Kristen and Ferreira, Juliana Bonin and Pairis-Garcia, Monique Danielle}, year={2023}, month={Jun} }
 @article{mercer_davis_mckenzie_messenger_schaefer_council-troche_werre_2023, title={Pharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.16663}, abstractNote={Acetaminophen has been evaluated in horses for treatment of musculoskeletal pain but not as an antipyretic.To determine the pharmacokinetics and efficacy of acetaminophen compared to placebo and flunixin meglumine in adult horses with experimentally induced endotoxemia.Eight university owned research horses with experimentally induced endotoxemia.Randomized placebo controlled crossover study. Horses were treated with acetaminophen (30 mg/kg PO; APAP), flunixin meglumine (1.1 mg/kg, PO; FLU), and placebo (PO; PLAC) 2 hours after administration of LPS. Plasma APAP was analyzed via LC-MS/MS. Serial CBC, lactate, serum amyloid A, heart rate and rectal temperature were evaluated. Serum IL-1β, IL-6, IL-8, IL-10, and TNF-α were evaluated by an equine-specific multiplex assay.Mean maximum plasma APAP concentration was 13.97 ± 2.74 μg/mL within 0.6 ± 0.3 hour after administration. At 4 and 6 hours after treatment, both APAP (P = <.001, P = .03, respectively) and FLU (P = .0045 and P < .001, respectively) had a significantly greater decrease in rectal temperature compared to placebo. FLU caused greater heart rate reduction than APAP at 4 and 6 hours (P = .004 and P = .04), and PLAC at 4 hours (P = .05) after treatment.The pharmacokinetics of acetaminophen in endotoxemic horses differ from those reported by previous studies in healthy horses. Acetaminophen is an option for antipyresis in clinical cases, particularly when administration of traditional NSAIDs is contraindicated.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Mercer, Melissa A. and Davis, Jennifer L. and McKenzie, Harold C. and Messenger, Kristen M. and Schaefer, Emily and Council-Troche, R. McAlister and Werre, Stephen R.}, year={2023}, month={Feb} }
 @article{shippy_allgood_messenger_hernandez_gatson_bustamante_alexander_wellehan jr_johnson_2023, title={Pharmacokinetics and pharmacodynamics of intramuscular alfaxalone in central bearded dragons (Pogona vitticeps): effect of injection site}, volume={50}, ISSN={["1467-2995"]}, DOI={10.1016/j.vaa.2023.02.010}, abstractNote={To evaluate the pharmacodynamic effects and pharmacokinetics of a single intramuscular (IM) injection of alfaxalone in central bearded dragons (Pogona vitticeps) when injected at a cranial versus a caudal site.Prospective, masked, randomized crossover study.A total of 13 healthy bearded dragons weighing 0.48 ± 0.1 kg.Alfaxalone (10 mg kg-1) was administered IM to 13 bearded dragons in the triceps muscle (cranial treatment) or the quadriceps muscle (caudal treatment) separated by 4 weeks. Pharmacodynamic variables included movement score, muscle tone score and righting reflex. Blood was obtained from the caudal tail vein using a sparse sampling methodology. Plasma alfaxalone concentrations were determined using liquid chromatography-mass spectrometry, and pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. Differences in variables between injection sites were analyzed using a nonparametric Wilcoxon signed-rank test for paired data with significance set at p ≤ 0.05.Time to loss of righting reflex score was not different, median (interquartile range), between cranial and caudal treatments [8 (5-11) and 8 (4-12) minutes, respectively, p = 0.72]. Time to recovery of righting reflex was also not different between cranial and caudal treatments [80 (44-112) and 64 (56-104) minutes, respectively, p = 0.75]. Plasma alfaxalone concentrations were not significantly different between treatments. The population estimate (95% confidence intervals) for volume of distribution per fraction absorbed was 1.0 (0.79-1.20) L kg-1, clearance per fraction absorbed was 9.6 (7.6-11.6) mL minute-1 kg-1, absorption rate constant was 2.3 (1.9-2.8) minute-1 and elimination half-life was 71.9 (52.7-91.1) minutes.Regardless of the injection site, IM alfaxalone (10 mg kg-1) produced reliable chemical restraint in central bearded dragons, appropriate for nonpainful diagnostic procedures or anesthetic premedication.}, number={3}, journal={VETERINARY ANAESTHESIA AND ANALGESIA}, author={Shippy, Sarah and Allgood, Hillary and Messenger, Kristen and Hernandez, Jorge A. and Gatson, Bonnie and Bustamante, Michelle G. Martin and Alexander, Amy B. and Wellehan Jr, James F. X. and Johnson, Alanna}, year={2023}, month={May}, pages={280–288} }
 @article{papich_madsen_messenger_enomoto_2022, title={Ceftazidime pharmacokinetics in dogs after intravenous injection and delivered with the RxActuator Mini-Infuser infusion pump}, volume={5}, ISSN={["1476-4431"]}, url={https://doi.org/10.1111/vec.13205}, DOI={10.1111/vec.13205}, abstractNote={Abstract Objective To test the feasibility of an SC mini‐infusion pump to deliver ceftazidime in dogs and produce plasma concentrations sufficient to reach a therapeutic target for 48 hours. Setting University research laboratory. Animals Six healthy Beagle dogs. Interventions Ceftazidime was administered by 2 routes to 6 healthy Beagle dogs. The first route was an IV bolus injection into a cephalic vein at a dose of 25 mg/kg. Blood samples were collected for 8 hours following injection. The second route was a SC infusion for 48 hours using the RxActuator Mini‐Infuser wearable SC constant rate infusion pump. Blood samples were collected for 58 hours following application of the pump. All plasma samples were analyzed by high‐pressure liquid chromatography and subject to pharmacokinetic analysis. Main Results After the IV bolus injection, there was rapid distribution and elimination. The elimination half‐life was 0.95 hours, and the clearance was rapid at 0.176 ml/h/kg. After the 48‐hour SC infusion, the half‐life was slightly shorter, and the clearance was higher. The percent bioavailability from the SC infusion was approximately 72%. The SC infusion maintained plasma concentration near our target of 8 μg/ml for most of the dose interval but slightly lower after 24 hours. The concentrations below the target were attributed to slight drug loss, less than 100% bioavailability, and faster clearance from SC administration. Conclusions This study demonstrated the successful application of the RxActuator Mini‐Infuser wearable SC constant rate infusion pump for delivering an antimicrobial needed for serious, and sometimes resistant, infections in dogs.}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={Papich, Mark G. and Madsen, Melanie and Messenger, Kristen and Enomoto, Hiroko}, year={2022}, month={May} }
 @article{madsen_enomoto_messenger_papich_2022, title={Effects of housing environment on oral absorption of acetaminophen in healthy Beagles}, volume={83}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.21.06.0075}, abstractNote={To evaluate the effects of housing environment on oral absorption of acetaminophen in dogs.6 healthy Beagles.Acetaminophen (325 mg, PO; mean dose, 31.1 mg/kg) was administered in a crossover study design with dogs housed in their normal environment or in a cage in an unfamiliar environment. There was a 7-day washout period between phases. Blood samples were collected for 24 hours following acetaminophen administration, and plasma acetaminophen concentrations were determined with high-pressure liquid chromatography.A 2-compartment model with lag time was the best fit for both phases of the study. None of the primary or secondary pharmacokinetic parameters were significantly different between the 2 housing environments.Findings suggested that in dogs, housing environment (normal environment vs a cage in an unfamiliar environment) did not significantly affect oral absorption and, by extension, gastric emptying of acetaminophen.}, number={1}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Madsen, Melanie and Enomoto, Hiroko and Messenger, Kristen and Papich, Mark G.}, year={2022}, month={Jan}, pages={80–85} }
 @article{koch_berglund_messenger_gilbertie_ellis_schnabel_2022, title={Interleukin-1β in tendon injury enhances reparative gene and protein expression in mesenchymal stem cells}, volume={9}, ISSN={2297-1769}, url={http://dx.doi.org/10.3389/fvets.2022.963759}, DOI={10.3389/fvets.2022.963759}, abstractNote={Tendon injury in the horse carries a high morbidity and monetary burden. Despite appropriate therapy, reinjury is estimated to occur in 50-65% of cases. Although intralesional mesenchymal stem cell (MSC) therapy has improved tissue architecture and reinjury rates, the mechanisms by which they promote repair are still being investigated. Additionally, reevaluating our application of MSCs in tendon injury is necessary given recent evidence that suggests MSCs exposed to inflammation (deemed MSC licensing) have an enhanced reparative effect. However, applying MSC therapy in this context is limited by the inadequate quantification of the temporal cytokine profile in tendon injury, which hinders our ability to administer MSCs into an environment that could potentiate their effect. Therefore, the objectives of this study were to define the temporal cytokine microenvironment in a surgically induced model of equine tendon injury using ultrafiltration probes and subsequently evaluate changes in MSC gene and protein expression following in vitro inflammatory licensing with cytokines of similar concentration as identified in vivo. In our in vivo surgically induced tendon injury model, IL-1β and IL-6 were the predominant pro-inflammatory cytokines present in tendon ultrafiltrate where a discrete peak in cytokine concentration occurred within 48 h following injury. Thereafter, MSCs were licensed in vitro with IL-1β and IL-6 at a concentration identified from the in vivo study; however, only IL-1β induced upregulation of multiple genes beneficial to tendon healing as identified by RNA-sequencing. Specifically, vascular development, ECM synthesis and remodeling, chemokine and growth factor function alteration, and immunomodulation and tissue reparative genes were significantly upregulated. A significant increase in the protein expression of IL-6, VEGF, and PGE2 was confirmed in IL-1β-licensed MSCs compared to naïve MSCs. This study improves our knowledge of the temporal tendon cytokine microenvironment following injury, which could be beneficial for the development and determining optimal timing of administration of regenerative therapies. Furthermore, these data support the need to further study the benefit of MSCs administered within the inflamed tendon microenvironment or exogenously licensed with IL-1β in vitro prior to treatment as licensed MSCs could enhance their therapeutic benefit in the healing tendon.}, journal={Frontiers in Veterinary Science}, publisher={Frontiers Media SA}, author={Koch, Drew W. and Berglund, Alix K. and Messenger, Kristen M. and Gilbertie, Jessica M. and Ellis, Ilene M. and Schnabel, Lauren V.}, year={2022}, month={Aug} }
 @article{bini_cohen_chiavaccini_messenger_bailey_2022, title={Intravenous dexmedetomidine, morphine, or a combination can result in gallbladder wall thickening; with no significant association with plasma histamine concentrations}, volume={1}, ISSN={["1740-8261"]}, url={https://doi.org/10.1111/vru.13056}, DOI={10.1111/vru.13056}, abstractNote={Abstract The gallbladder is routinely evaluated during ultrasonographic examinations in dogs. However, published studies describing the effects of sedative agents on gallbladder wall thickness are currently lacking. The aims of this prospective, blinded, randomized crossover pilot study were to test hypotheses that IV morphine would result in gallbladder wall thickening, that morphine administration would increase plasma histamine concentrations, and that combining IV morphine with dexmedetomidine would potentiate gallbladder wall thickening. Six healthy Beagle dogs were sedated with intravenous (IV) morphine 0.4 mg/kg (group M), dexmedetomidine 7 μg/kg (group D), or a combination of the two (group MD). Physiologic parameters were measured at baseline and at regular intervals until the last ultrasonographic scan. Ultrasonographic scans were performed at baseline, 90 s, and at 5, 15, 30, 45, 60, 90, and 120 min. Plasma histamine samples were taken at baseline, 90 s, and 5 and 60 min. Cochran's Q ‐test was used to compare gallbladder wall thickening between groups, while the association between histamine plasma concentration and gallbladder wall thickness was compared with a mixed‐effects model. Baseline gallbladder wall thickness was not significantly different between groups. Six of 18 treatments/dogs (33%) developed gallbladder thickening, with no difference between groups. There was no significant difference in baseline plasma histamine concentrations between groups, and no association between plasma histamine concentration and gallbladder wall thickness. Gallbladder wall thickening was observed in at least one dog in each group, therefore caution is recommended for gallbladder wall thickness ultrasonographic interpretation in dogs when these drugs have been administered.}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, publisher={Wiley}, author={Bini, Gianluca and Cohen, Eli B. and Chiavaccini, Ludovica and Messenger, Kristen M. and Bailey, Kate M.}, year={2022}, month={Jan} }
 @article{mancini_early_slater_olby_mariani_munana_woelfel_schacher_zhong_messenger_2022, title={Novel subcutaneous cytarabine infusion with the Omnipod system in dogs with meningoencephalomyelitis of unknown etiology}, volume={83}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.22.03.0046}, abstractNote={Abstract OBJECTIVE To investigate the feasibility and pharmacokinetics of cytarabine delivery as a subcutaneous continuous-rate infusion with the Omnipod system. ANIMALS 6 client-owned dogs diagnosed with meningoencephalomyelitis of unknown etiology were enrolled through the North Carolina State University Veterinary Hospital. PROCEDURES Cytarabine was delivered at a rate of 50 mg/m 2 /hour as an SC continuous-rate infusion over 8 hours using the Omnipod system. Plasma samples were collected at 0, 4, 6, 8, 10, 12, and 14 hours after initiation of the infusion. Plasma cytarabine concentrations were measured by high-pressure liquid chromatography. A nonlinear mixed-effects approach generated population pharmacokinetic parameter estimates. RESULTS The mean peak plasma concentration (Cmax) was 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL), average time to Cmax was 7 hours (range, 4 to 8 hours; SD, 1.67 hours), terminal half-life was 1.13 hours (SD, 0.29 hour), and the mean area under the curve was 52,996.82 hours X μg/mL (range, 35,963.67 to 71,848.37 hours X μg/mL; SD, 12,960.90 hours X μg/mL). Cmax concentrations for all dogs were more than 1,000 ng/mL (1.0 μg/mL) at the 4-, 6-, 8-, and 10-hour time points. CLINICAL RELEVANCE An SC continuous-rate infusion of cytarabine via the Omnipod system is feasible in dogs and was able to achieve a steady-state concentration of more than 1 μg/mL 4 to 10 hours postinitiation of cytarabine and a Cmax of 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL). These are comparable to values reported previously with IV continuous-rate infusion administration in healthy research Beagles and dogs with meningoencephalomyelitis of unknown etiology.}, number={9}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Mancini, Shelby L. and Early, Peter J. and Slater, Bailey M. and Olby, Natasha J. and Mariani, Christopher L. and Munana, Karen R. and Woelfel, Christian W. and Schacher, Jordan A. and Zhong, Li and Messenger, Kristen M.}, year={2022}, month={Sep} }
 @article{nixon_chittenden_baynes_messenger_2022, title={Pharmacokinetic/pharmacodynamic modeling of ketoprofen and flunixin at piglet castration and tail-docking}, volume={7}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/jvp.13083}, DOI={10.1111/jvp.13083}, abstractNote={Abstract This study performed population‐pharmacokinetic/pharmacodynamic (pop‐PK/PD) modeling of ketoprofen and flunixin in piglets undergoing routine castration and tail‐docking, utilizing previously published data. Six‐day‐old male piglets (8/group) received either ketoprofen (3.0 mg/kg) or flunixin (2.2 mg/kg) intramuscularly. Two hours post‐dose, piglets were castrated and tail docked. Inhibitory indirect response models were developed utilizing plasma cortisol or interstitial fluid prostaglandin E2 (PGE2) concentration data. Plasma IC50 for ketoprofen utilizing PGE2 as a biomarker was 1.2 μg/ml, and ED50 for was 5.83 mg/kg. The ED50 calculated using cortisol was 4.36 mg/kg; however, the IC50 was high, at 2.56 μg/ml. A large degree of inter‐individual variability (124.08%) was also associated with the cortisol IC50 following ketoprofen administration. IC50 for flunixin utilizing cortisol as a biomarker was 0.06 μg/ml, and ED50 was 0.51 mg/kg. The results show that the currently marketed doses of ketoprofen (3.0 mg/kg) and flunixin (2.2 mg/kg) correspond to drug responses of 33.97% (ketoprofen‐PGE2), 40.75% (ketoprofen‐cortisol), and 81.05% (flunixin‐cortisol) of the maximal possible responses. Given this information, flunixin may be the best NSAID to use in mitigating castration and tail‐docking pain at the current label dose.}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, publisher={Wiley}, author={Nixon, Emma and Chittenden, Jason T. and Baynes, Ronald E. and Messenger, Kristen M.}, year={2022}, month={Jul} }
 @article{enomoto_love_madsen_wallace_messenger_2022, title={Pharmacokinetics of intravenous, oral transmucosal, and intranasal buprenorphine in healthy male dogs}, volume={7}, ISSN={["1365-2885"]}, url={http://europepmc.org/abstract/med/35445748}, DOI={10.1111/jvp.13056}, abstractNote={Abstract Effective management of pain in animals is of critical importance but options are limited for treating acute pain in dogs on an outpatient basis. The objective of this study was to compare the plasma concentrations and pharmacokinetics of a concentrated solution of buprenorphine, 1.8 mg/ml (Simbadol™) administered intravenously, intranasally, and via the oral transmucosal (OTM) route in healthy male dogs. Five healthy castrated adult male Beagle‐cross dogs were included in this randomized blocked crossover study. The dogs received 0.03 mg/kg body weight buprenorphine intravenously, intranasally, or via the OTM route, with a minimum 72‐h washout period between treatments. Blood samples were collected at multiple intervals up to 24 h post administration and buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. Non‐compartmental pharmacokinetic analysis revealed that the area under the curve of intravenous, intranasal, and OTM routes were 28.0 (15.1–41.3) h × ng/ml, 16.1 (3.4–28.7) h × ng/ml and 10.8 (8.8–11.8) h × ng/ml, respectively. The bioavailability of intranasal and OTM routes were 57.5 (22.7–93.7)% and 41.1 (25.5–69.4)%, respectively. Intranasal and OTM routes of administration of concentrated buprenorphine in dogs may allow for the provision of analgesic care at home.}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Enomoto, Hiroko and Love, Lydia and Madsen, Melanie and Wallace, Amber and Messenger, Kristen M.}, year={2022}, month={Apr} }
 @article{southern_long_barnes_enomoto_messenger_2022, title={Preliminary evaluation of the effects of grapiprant compared with carprofen on acute pain and inflammation following ovariohysterectomy in dogs}, volume={83}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.21.10.0162}, abstractNote={Abstract OBJECTIVE To compare the analgesic efficacy of grapiprant to carprofen for the treatment of postoperative pain and inflammation in dogs following ovariohysterectomy. ANIMALS 12 purpose-bred adult sexually intact female Beagles. PROCEDURES Dogs were randomly assigned to 1 of 2 treatment groups: grapiprant (2 mg/kg, PO; n = 6) or carprofen (4.4 mg/kg, PO; n = 6), 1.5 hours prior to ovariohysterectomy (OVH) and every 24 hours afterward for 3 total doses. An ultrafiltration probe was placed within the OVH incision to collect interstitial fluid (ISF). Pain and inflammation were assessed by masked investigators via mechanical nociceptive threshold testing and the short form of the Glasgow Composite Pain Scale before drug administration and at multiple time points for 72 hours following dosing and surgery. ISF samples were collected at the same time points to assess prostaglandin E 2 concentrations at the site of inflammation. RESULTS In both groups, pain scale scores were highest in the immediate postoperative period and decreased over time. In both treatment groups, there were significant ( P = 0.003) differences in mechanical nociceptive threshold results over time when compared with baseline, but there was no difference between groups. Prostaglandin E 2 concentrations in ISF were higher in dogs receiving grapiprant compared with carprofen ( P < 0.001). One dog in the carprofen group required rescue analgesia. CLINICAL RELEVANCE Results of this preliminary study suggested both carprofen and grapiprant may be effective for postoperative pain following OVH in dogs; however, additional studies are warranted to determine grapiprant’s effectiveness in a larger and more diverse population of dogs.}, number={7}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Southern, Brittany L. and Long, Sarah M. and Barnes, Danielle N. and Enomoto, Hiroko and Messenger, Kristen M.}, year={2022}, month={Jul} }
 @article{chang_barletta_messenger_sakai_reed_quandt_2022, title={The effect of a ketamine constant rate infusion on cardiovascular variables in sheep anesthetized at the minimum alveolar concentration of sevoflurane that blunts adrenergic responses}, volume={83}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.21.08.0129}, abstractNote={Abstract OBJECTIVE To evaluate the effect of a constant rate infusion of ketamine on cardiac index (CI) in sheep, as estimated using noninvasive cardiac output (NICO) monitoring by partial carbon dioxide rebreathing, when anesthetized with sevoflurane at the previously determined minimum alveolar concentration that blunts adrenergic responses (MAC BAR ). ANIMALS 12 healthy Dorset-crossbred adult sheep. PROCEDURES Sheep were anesthetized 2 times in a balanced placebo-controlled crossover design. Anesthesia was induced with sevoflurane delivered via a tight-fitting face mask and maintained at MAC BAR . Following induction, sheep received either ketamine (1.5 mg/kg IV, followed by a constant rate infusion of 1.5 mg/kg/h) or an equivalent volume of saline (0.9% NaCl) solution (placebo). After an 8-day washout period, each sheep received the alternate treatment. NICO measurements were performed in triplicate 20 minutes after treatment administration and were converted to CI. Blood samples were collected prior to the start of NICO measurements for analysis of ketamine plasma concentrations. The paired t test was used to compare CI values between groups and the ketamine plasma concentrations with those achieved during the previous study. RESULTS Mean ± SD CI of the ketamine and placebo treatments were 2.69 ± 0.65 and 2.57 ± 0.53 L/min/m 2 , respectively. No significant difference was found between the 2 treatments. Mean ketamine plasma concentration achieved prior to the NICO measurement was 1.37 ± 0.58 µg/mL, with no significant difference observed between the current and prior study. CLINICAL RELEVANCE Ketamine, at the dose administered, did not significantly increase the CI in sheep when determined by partial carbon dioxide rebreathing.}, number={3}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Chang, Kevin and Barletta, Michele and Messenger, Kristen M. and Sakai, Daniel M. and Reed, Rachel A. and Quandt, Jane E.}, year={2022}, month={Mar}, pages={205–211} }
 @article{nixon_carlson_routh_hernandez_almond_baynes_messenger_2021, title={Comparative effects of nonsteroidal anti-inflammatory drugs at castration and tail-docking in neonatal piglets}, volume={16}, ISSN={["1932-6203"]}, url={https://doi.org/10.1371/journal.pone.0254409}, DOI={10.1371/journal.pone.0254409}, abstractNote={This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam (MEL; 0.4 mg/kg), flunixin (FLU; 2.2 mg/kg), ketoprofen (KETO; 3.0 mg/kg) or sham (SAL SHAM; saline injection, no processing). Two hours post-dose, piglets were castrated and tail-docked. Plasma cortisol, interstitial fluid (ISF) prostaglandin E2 (PGE2) and activity levels via Actical® monitoring were used to estimate pain. SAL SHAM and FLU exhibited lower cortisol concentrations than SAL PROC at the time of processing (p = 0.003 and p = 0.049, respectively), and all NSAIDs exhibited lower PGE2 than SAL PROC at 3.69 hours (MEL p = 0.050; FLU p = 0.043 and KETO p = 0.031). While not statistically significant, PGE2 was higher in SAL PROC piglets vs. other treatment groups at most time points. There was also a high degree of variability between piglets, especially for SAL PROC. Activity levels were significantly decreased at multiple time points in SAL PROC and MEL piglets following processing. However, FLU and KETO piglets had increased activity levels closer to that of the SAL SHAM group, suggesting that these NSAIDs are more effective than MEL in providing analgesia. These results demonstrate that management strategies including administration of intramuscular flunixin or ketoprofen to reduce pain associated with processing will likely improve piglet health and welfare in the United States.}, number={11}, journal={PLOS ONE}, author={Nixon, Emma and Carlson, Alexandra R. and Routh, Patricia A. and Hernandez, Liliana and Almond, Glen W. and Baynes, Ronald E. and Messenger, Kristen M.}, editor={Loor, Juan J.Editor}, year={2021}, month={Nov} }
 @article{enomoto_yeatts_carbajal_krishnan_madan_laumas_blikslager_messenger_2021, title={In vivo assessment of a delayed release formulation of larazotide acetate indicated for celiac disease using a porcine model}, volume={16}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0249179}, abstractNote={There is no FDA approved therapy for the treatment of celiac disease (CeD), aside from avoidance of dietary gluten. Larazotide acetate (LA) is a first in class oral peptide developed as a tight junction regulator, which is a lead candidate for management of CeD. A delayed release formulation was tested in vitro and predicted release in the mid duodenum and jejunum, the target site of CeD. The aim of this study was to follow the concentration versus time profile of orally administered LA in the small intestine using a porcine model. A sensitive liquid chromatography/tandem mass spectrometry method was developed to quantify LA concentrations in porcine intestinal fluid samples. Oral dosing of LA (1 mg total) in overnight fasted pigs resulted in time dependent appearance of LA in the distal duodenum and proximal jejunum. Peak LA concentrations (0.32–1.76 μM) occurred at 1 hour in the duodenum and in proximal jejunum following oral dosing, with the continued presence of LA (0.02–0.47 μM) in the distal duodenum and in proximal jejunum (0.00–0.43 μM) from 2 to 4 hours following oral dosing. The data shows that LA is available in detectable concentrations at the site of CeD.}, number={4}, journal={PLOS ONE}, author={Enomoto, Hiroko and Yeatts, James and Carbajal, Liliana and Krishnan, B. Radha and Madan, Jay P. and Laumas, Sandeep and Blikslager, Anthony T. and Messenger, Kristen M.}, year={2021}, month={Apr} }
 @article{slifer_hernandez_pridgen_carlson_messenger_madan_krishnan_laumas_blikslager_2021, title={Larazotide acetate induces recovery of ischemia-injured porcine jejunum via repair of tight junctions}, volume={16}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0250165}, abstractNote={Intestinal ischemia results in mucosal injury, including paracellular barrier loss due to disruption of tight junctions. Larazotide acetate (LA), a small peptide studied in Phase III clinical trials for treatment of celiac disease, regulates tight junctions (TJs). We hypothesized that LA would dose-dependently hasten recovery of intestinal ischemic injury via modulation of TJs. Ischemia-injured tissue from 6-8-week-old pigs was recovered in Ussing chambers for 240-minutes in the presence of LA. LA (1 μM but not 0.1 μM or 10 μM) significantly enhanced transepithelial electrical resistance (TER) above ischemic injured controls and significantly reduced serosal-to-mucosal flux LPS ( P<0 . 05 ). LA (1 μM) enhanced localization of the sealing tight junction protein claudin-4 in repairing epithelium. To assess for the possibility of fragmentation of LA, an in vitro enzyme degradation assay using the brush border enzyme aminopeptidase M, revealed generation of peptide fragments. Western blot analysis of total protein isolated from uninjured and ischemia-injured porcine intestine showed aminopeptidase M enzyme presence in both tissue types, and mass spectrometry analysis of samples collected during ex vivo analysis confirmed formation of LA fragments. Treatment of tissues with LA fragments had no effect alone, but treatment with a fragment missing both amino-terminus glycines inhibited barrier recovery stimulated by 1 μM LA. To reduce potential LA inhibition by fragments, a D-amino acid analog of larazotide Analog #6, resulted in a significant recovery response at a 10-fold lower dose (0.1 μM) similar in magnitude to that of 1 μM LA. We conclude that LA stimulates repair of ischemic-injured epithelium at the level of the tight junctions, at an optimal dose of 1 μM LA. Higher doses were less effective because of inhibition by LA fragments, which could be subverted by chirally-modifying the molecule, or microdosing LA.}, number={4}, journal={PLOS ONE}, author={Slifer, Zachary M. and Hernandez, Liliana and Pridgen, Tiffany A. and Carlson, Alexandra R. and Messenger, Kristen M. and Madan, Jay and Krishnan, B. Radha and Laumas, Sandeep and Blikslager, Anthony T.}, year={2021}, month={Apr} }
 @article{belda_ramos-vara_messenger_risselada_2021, title={Pharmacokinetic and safety assessment of carboplatin-impregnated calcium sulfate hemihydrate beads in eight rats}, ISSN={["1532-950X"]}, DOI={10.1111/vsu.13712}, abstractNote={Abstract Objective Evaluate local tissue toxicity and plasma platinum (Pt) in vivo after subcutaneous implantation of carboplatin‐impregnated calcium sulfate hemihydrate (CI‐CSH) beads. Study design In vivo experimental study. Animals Eight male Sprague–Dawley rats. Methods CI‐CSH beads were implanted subcutaneously (5 mg carboplatin/rat; 13.5 mg/kg carboplatin; 7.08 mg/kg Pt; 1.18 mg/m 2 Pt) in eight rats (d0). Wound healing (daily), radiographic bead dissolution (weekly), systemic Pt uptake (plasma‐Pt), local tissue Pt (d28), and histologic changes compared to nonincised and incised catheterization sites (d28) were assessed. Blood and tissue samples were analyzed by inductively coupled plasma mass spectrometry for Pt, and pharmacokinetic analysis was performed using noncompartmental methods. Results One rat died at d10, the remainder survived until d28. No wound complications were seen. The CI‐CSH implantation site had higher histopathology scores than the other sites for necrosis ( p = .013) and fibrosis ( p = .013). Beads decreased in density radiographically (d0 to d28) ( p = .062). Peak plasma‐Pt concentration was 225.78 ng/ml at 12 h, and decreased over time, but Pt was still detectable on d28. The elimination half‐life was 5.03 ± 1.13 days. Only 1.69% of implanted Pt remained in the beads at d28. Conclusions CI‐CSH beads incited microscopic mild inflammation but wound healing was not impaired. Pt was absorbed systemically and the release from the beads was near complete at d28. Clinical significance Piled CI‐CSH bead implantation is well tolerated in rats with similar elution profile as previously described. Beads were radiographically visible at d28. Minimal Pt was detected systemically suggesting Pt release does not match bead dissolution.}, journal={VETERINARY SURGERY}, author={Belda, Beatriz and Ramos-Vara, Jose and Messenger, Kristen M. and Risselada, Marije}, year={2021}, month={Aug} }
 @article{tracy_lynch_messenger_vaden_vigani_2021, title={Use of extracorporeal therapy in a dog with heatstroke}, volume={32}, ISSN={1479-3261 1476-4431}, url={http://dx.doi.org/10.1111/vec.13169}, DOI={10.1111/vec.13169}, abstractNote={To describe the use of extracorporeal therapy (ECT) in the management of a dog with complications stemming from heatstroke.A 3-year-old intact male Rhodesian Ridgeback was presented for heat-related illness following strenuous exercise. Despite intensive supportive care, the dog developed progressive and refractory hyperkalemia, hypoglycemia, neurologic dysfunction, acute kidney injury (AKI), and pulmonary dysfunction. Four ECT sessions were performed in this dog, consisting of 4 intermittent hemodialysis (HD) sessions, the first 2 of which concurrently utilized hemoperfusion with a cytokine adsorption filter. Interleukin-6 (IL-6), IL-8, IL-10, and monocyte chemoattractant protein-1 were detected in samples collected during the first ECT session. Despite an initial decrease in their concentration, the concentrations of these cytokines ultimately rose over the course of the ECT session. Rapid and sustained glycemic and electrolyte control were achieved after the first ECT session, although AKI and muscle injury persisted. The dog survived to discharge and was nonazotemic 3 months following initial management.Heatstroke is a common, potentially catastrophic, occurrence in dogs. To the authors' knowledge, this represents the first clinical use of ECT consisting of HD and cytokine adsorption in the management of severe heat-related illness in a dog. The use of ECT for the management of complications from severe heatstroke in dogs warrants further investigation.}, number={4}, journal={Journal of Veterinary Emergency and Critical Care}, publisher={Wiley}, author={Tracy, Alyx and Lynch, Alex and Messenger, Kristen and Vaden, Shelly and Vigani, Alessio}, year={2021}, month={Dec}, pages={512–519} }
 @article{nixon_almond_baynes_messenger_2020, title={Comparative Plasma and Interstitial Fluid Pharmacokinetics of Meloxicam, Flunixin, and Ketoprofen in Neonatal Piglets}, volume={7}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2020.00082}, abstractNote={Piglet castration and tail-docking are routinely performed in the United States without analgesia. Pain medications, predominately non-steroidal anti-inflammatory drugs, are used in the EU/Canada to decrease pain associated with processing and improve piglet welfare, however, past studies have shown the efficacy and required dose remain controversial, particularly for meloxicam. This study assessed the pharmacokinetics of three NSAIDs (meloxicam, flunixin, and ketoprofen) in piglets prior to undergoing routine castration and tail-docking. Five-day-old male piglets (8/group) received one of 3 randomized treatments; meloxicam (0.4 mg/kg), flunixin (2.2 mg/kg), ketoprofen (3.0 mg/kg). Two hours post-dose, piglets underwent processing. Drug concentrations were quantified in plasma and interstitial fluid (ISF) and pharmacokinetic parameters were generated by non-compartmental analysis. Time to peak concentration (Tmax) of meloxicam, flunixin, and S(-)-ketoprofen in plasma were 1.21, 0.85, and 0.59 h, compared to 2.81, 3.64, and 2.98 h in the ISF, respectively. The apparent terminal half-life of meloxicam, flunixin and S(-)-ketoprofen were 4.39, 7.69, and 3.50 h, compared to 11.26, 16.34, and 5.54 h, respectively in the ISF. If drug concentrations in the ISF are more closely related to efficacy than the plasma, then the delay between the Tmax in plasma and ISF may be relevant to the timing of castration in order to provide the greatest analgesic effect.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Nixon, Emma and Almond, Glen W. and Baynes, Ronald E. and Messenger, Kristen M.}, year={2020}, month={Feb} }
 @article{barletta_quandt_reed_hofmeister_messenger_2020, title={Determination of the minimum alveolar concentration of sevoflurane that blunts adrenergic responses and the effect of a constant rate infusion of ketamine in sheep}, volume={128}, ISSN={["1532-2661"]}, DOI={10.1016/j.rvsc.2019.12.011}, abstractNote={Minimizing sympathetic stimulation under anesthesia prevents activation of the neuroendocrine stress response. The minimum alveolar concentration blunting adrenergic responses in 50% of the population when exposed to a noxious stimulus is defined as MAC-BAR. The purpose of this study was to determine the MAC-BAR of sevoflurane (MAC-BARsevo) in sheep and the MAC-BAR sparing effects of ketamine. Thirteen healthy Dorset-cross adult ewes, 4 ± 1 year old and weighing 74 ± 9 kg, were enrolled in a randomized blinded crossover study design. Ewes were anesthetized twice for MAC-BARsevo determination. After face mask induction with sevoflurane, sheep received intravenous ketamine at 1.5 mg/kg and a constant rate infusion of 1.5 mg/kg/h or an equivalent volume of saline (placebo). After 8 day washout, the other treatment was administered. A bracketing technique was used for MAC-BARsevo determination and values were collected in duplicate. The mechanical stimulus (sponge forceps) was applied at the coronary band for 1 min and blood was collected for ketamine plasma concentrations. The MAC-BARsevo values of each treatment were compared using a paired t-test. Mean MAC-BARsevo of the ketamine and placebo were 2.73 ± 0.23% and 2.77 ± 0.31%, respectively and no significant difference was found (p = .638). Average ketamine plasma concentrations was 1.54 ± 0.18 μg/mL maintained through the study. Ketamine at 1.5 mg/kg, followed by 1.5 mg/kg/h, did not decrease the MAC-BARsevo in sheep. Further studies to determine the effect of higher doses of ketamine on inhalational anesthetic agents and their potential adverse effects are warranted.}, journal={RESEARCH IN VETERINARY SCIENCE}, author={Barletta, Michele and Quandt, Jane E. and Reed, Rachel A. and Hofmeister, Erik H. and Messenger, Kristen M.}, year={2020}, month={Feb}, pages={230–235} }
 @article{fick_messenger_vigani_2020, title={Efficacy of a single session in-series hemoperfusion and hemodialysis in the management of carprofen overdose in two dogs}, volume={30}, ISSN={["1476-4431"]}, DOI={10.1111/vec.12931}, abstractNote={To describe the efficacy of in-series hemoperfusion and hemodialysis in 2 dogs with carprofen overdose.This report describes the treatment of 2 dogs following accidental carprofen overdoses who underwent a single in-series hemoperfusion and hemodialysis session. Serial serum carprofen concentrations were measured before, during, and after the session. The first patient's session lasted 5 hours, with the largest decrease in serum carprofen concentrations occurring during the first hour of treatment. The carprofen clearance during the following 4 hours of treatment decreased substantially compared to the first hour and was not different from the patient's intrinsic clearance of carprofen after the session was completed. Based on the findings from the first case, the second patient was treated with a 1 hour single hemoperfusion and hemodialysis session. Our results support the hypothesis that carprofen is not effectively removed by conventional hemodialysis and the efficacy of hemoperfusion is short lived due to rapid saturation of the charcoal filter. Once filter saturation occurs, the extracorporeal session is no longer efficacious. Using in-series hemoperfusion and hemodialysis is of benefit to correct the side effects seen with hemoperfusion alone, and hourly charcoal filter replacement may extend the efficacy of treatment in removing carprofen.This is the first published report of in-series hemoperfusion and hemodialysis being used to treat carprofen overdose in a dog. In these 2 cases, the intrinsic clearances of the patients were shown to be equivalent to that of standard hemodialysis alone, indicating that hemodialysis does not produce any advantage in carprofen clearance. In this limited report, we suggest that the efficacy of hemoperfusion in removing carprofen is short-lived, and extending the treatment beyond the first hour does not produce any therapeutic benefit. In order to extend the efficacy of hemoperfusion, hourly replacement of the charcoal filter should be considered.}, number={2}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={Fick, Meghan E. and Messenger, Kristen M. and Vigani, Alessio}, year={2020}, month={Mar}, pages={226–231} }
 @article{smith_tolbert_gould_taylor_knych_messenger_2020, title={Pharmacokinetics, sedation and hemodynamic changes following the administration of oral transmucosal detomidine gel in cats}, volume={22}, ISSN={["1532-2750"]}, DOI={10.1177/1098612X20917305}, abstractNote={Objectives The aim of this study was to describe the pharmacokinetics of oral transmucosal (OTM) detomidine gel in healthy cats and assess its effects on sedation and hemodynamic variables. Methods Eight adult cats weighing 4.12 kg ± 0.72 received 4 mg/m 2 detomidine gel onto the buccal mucosa. Level of sedation, heart rate (HR), blood pressure (BP) and respiratory rate ( f R) were assessed at predetermined intervals following administration. Blood samples for plasma detomidine concentrations and venous blood gas variables were collected from a medial saphenous catheter. Plasma detomidine concentrations were analyzed using ultra-high-pressure liquid chromatography with mass spectrometry detection, and pharmacokinetic estimates were obtained with compartmental methods. Data were analyzed using ANOVA and paired t-test or appropriate non-parametric tests. Results Sedation occurred in all cats, and was increased from baseline at 30 mins ( P <0.001). Decreases in HR occurred from 15–60 mins, ranging from 140 to 165 beats per min ( P <0.001). Blood glucose increased from 101 ± 12 mg/dl to 168 ± 27.3 mg/dl at 60 mins ( P = 0.004). Systolic blood pressure decreased from baseline (139 ± 14.8 mmHg) to 103 ± 23.0 mmHg at 60 mins ( P = 0.023). All changes abated by 120 mins. Emesis occurred in 7/7 cats within 2 mins of gel administration. Geometric mean (coefficient of variation) for clearance was 220.7 ml/min/kg (35.3 ml/min/kg), volume of distribution was 14.9 l/kg (39.9 l/kg) (both a function of bioavailability) and elimination half-life was 46.9 mins (16.0 mins). Maximum plasma concentrations of 10.5 ng/ml (35.5 ng/ml) detomidine occurred at 36.9 mins (21.5 mins). Conclusions and relevance OTM detomidine gel produced moderate sedation with minimal undesirable side effects in healthy cats, although emesis occurred in all cats. The pharmacokinetic profile supports short-term, minimally invasive sedation in this species. Further studies are warranted to assess its safety and feasibility for use in debilitated cats, or prior to general anesthesia.}, number={12}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Smith, Preston and Tolbert, M. Katherine and Gould, Emily and Taylor, Alex and Knych, Heather and Messenger, Kristen}, year={2020}, month={Dec}, pages={1184–1190} }
 @article{carlson_nixon_jacob_messenger_2020, title={Sterility and concentration of liposomal bupivacaine single-use vial when used in a multiple-dose manner}, volume={49}, ISSN={["1532-950X"]}, DOI={10.1111/vsu.13380}, abstractNote={Abstract Objective To evaluate the sterility of bupivacaine liposome injectable suspension (Nocita®) used in a multiple‐dose fashion for 5 days. Study design Triplicate liposomal bupivacaine vials were stored under two conditions, (1) room temperature (24°C) and (2) refrigerated temperature (5°C). A 3‐mL aliquot was withdrawn from each vial daily. Samples were inoculated in tryptic soy broth in triplicate and then incubated for 24 hours at 37°C and subcultured every 48 hours onto blood agar and Sabouraud dextrose agar, respectively. Separate 1.5‐mL aliquots of liposomal bupivacaine were centrifuged at 3500 g to separate liposome‐encapsulated bupivacaine from the solution. Concentration of unencapsulated bupivacaine was analyzed via high‐pressure liquid chromatography. Data were analyzed by using mixed effects procedure with multiple comparisons. Sample population Ten 20‐mL vials of bupivacaine liposome injectable suspension stored under two conditions, (1) room temperature (24°C) and (2) refrigerated temperature (5°C). Results Five days of repeated withdrawal from the single‐use vials yielded no bacterial growth. One control vial, which was opened and punctured once on the last day of the experiment, yielded fungal growth of an Aspergillus spp, likely an environmental contaminant. The concentration of free bupivacaine did not significantly differ until the fifth day of sampling. Conclusion When aseptic technique was used, liposomal bupivacaine remained sterile for 5 days. Concentrations of free bupivacaine were unchanged from baseline for 4 days in both refrigerated and room temperature conditions. Clinical significance Single‐use liposomal bupivacaine vials can be used extralabel in a multiple‐dose fashion for up to 4 days when stored either refrigerated or room temperature when sterile technique is used.}, number={4}, journal={VETERINARY SURGERY}, author={Carlson, Alexandra R. and Nixon, Emma and Jacob, Megan E. and Messenger, Kristen M.}, year={2020}, month={May}, pages={772–777} }
 @article{bennett_seddighi_moorhead_messenger_cox_sun_pasloske_pypendop_doherty_2019, title={Effect of fentanyl on the induction dose and minimum infusion rate of alfaxalone preventing movement in dogs}, volume={46}, ISSN={["1467-2995"]}, DOI={10.1016/j.vaa.2018.10.006}, abstractNote={To determine the effect of fentanyl on the induction dose and minimum infusion rate of alfaxalone required to prevent movement in response to a noxious stimulus (MIRNM) in dogs.Experimental crossover design.A group of six healthy, adult, intact female mixed-breed dogs, weighing 19.7 ± 1.3 kg.Dogs were randomly administered one of three treatments at weekly intervals: premedication with 0.9% saline (treatment A), fentanyl 5 μg kg-1 (treatment ALF) or fentanyl 10 μg kg-1 (treatment AHF), administered intravenously over 5 minutes. Anesthesia was induced 5 minutes later with incremental doses of alfaxalone to achieve intubation and was maintained for 90 minutes in A with alfaxalone (0.12 mg kg-1 minute-1), in ALF with alfaxalone (0.09 mg kg-1 minute-1) and fentanyl (0.1 μg kg-1 minute-1) and in AHF with alfaxalone (0.06 mg kg-1 minute-1) and fentanyl (0.2 μg kg-1 minute-1). The alfaxalone infusion was increased or decreased by 0.006 mg kg-1 minute-1 based on positive or negative response to antebrachium stimulation (50 V, 50 Hz, 10 ms). Data were analyzed using a mixed-model anova and presented as least squares means ± standard error.Alfaxalone induction doses were 3.50 ± 0.13 (A), 2.17 ± 0.10 (ALF) and 1.67 ± 0.10 mg kg-1 (AHF) and differed among treatments (p < 0.05). Alfaxalone MIRNM was 0.17 ± 0.01 (A), 0.10 ± 0.01 (ALF) and 0.07 ± 0.01 mg kg-1 minute-1 (AHF) and differed among treatments. ALF and AHF decreased the MIRNM by 44 ± 8% and 62 ± 5%, respectively (p < 0.05). Plasma alfaxalone concentrations at MIRNM were 5.82 ± 0.48 (A), 4.40 ± 0.34 (ALF) and 2.28 ± 0.09 μg mL-1 (AHF).Fentanyl, at the doses studied, significantly decreased the alfaxalone induction dose and MIRNM.}, number={2}, journal={VETERINARY ANAESTHESIA AND ANALGESIA}, author={Bennett, Katherine J. and Seddighi, Reza and Moorhead, Kaitlin A. and Messenger, Kristin and Cox, Sherry K. and Sun, Xiaocun and Pasloske, Kirby and Pypendop, Bruno H. and Doherty, Thomas J.}, year={2019}, month={Mar}, pages={173–181} }
 @article{kruse_messenger_bowman_aarnes_wittum_flint_2019, title={Pharmacokinetics and pharmacodynamics of alfaxalone after a single intramuscular or intravascular injection in mallard ducks (Anas platyrhynchos)}, volume={42}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12804}, abstractNote={Pharmacokinetics and pharmacodynamics of alfaxalone was performed in mallard ducks (Anas platyrhynchos) after single bolus injections of 10 mg/kg administered intramuscularly (IM; n = 10) or intravenously (IV; n = 10), in a randomized cross-over design with a washout period between doses. Mean (±SD) Cmax following IM injection was 1.6 (±0.8) µg/ml with Tmax at 15.0 (±10.5) min. Area under the curve (AUC) was 84.66 and 104.58 min*mg/ml following IV and IM administration, respectively. Volume of distribution (VD ) after IV dose was 3.0 L/kg. The mean plasma clearance after 10 mg/kg IV was 139.5 (±67.9) ml min-1 kg-1 . Elimination half-lives (mean [±SD]) were 15.0 and 16.1 (±3.0) min following IV and IM administration, respectively. Mean bioavailability at 10 mg/kg IM was 108.6%. None of the ducks achieved a sufficient anesthetic depth for invasive procedures, such as surgery, to be performed. Heart and respiratory rates measured after administration remained stable, but many ducks were hyperexcitable during recovery. Based on sedation levels and duration, alfaxalone administered at dosages of 10 mg/kg IV or IM in mallard ducks does not induce clinically acceptable anesthesia.}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Kruse, Tamara N. and Messenger, Kristen M. and Bowman, Andrew S. and Aarnes, Turi K. and Wittum, Thomas E. and Flint, Mark}, year={2019}, month={Nov}, pages={713–721} }
 @article{madsen_messenger_papich_2019, title={Pharmacokinetics of levofloxacin following oral administration of a generic levofloxacin tablet and intravenous administration to dogs}, volume={80}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.80.10.957}, abstractNote={Abstract OBJECTIVE To determine the pharmacokinetics of levofloxacin following oral administration of a generic levofloxacin tablet and IV administration to dogs and whether the achieved plasma levofloxacin concentration would be sufficient to treat susceptible bacterial infections. ANIMALS 6 healthy adult Beagles. PROCEDURES Levofloxacin was administered orally as a generic 250-mg tablet (mean dose, 23.7 mg/kg) or IV as a solution (15 mg/kg) to each dog in a crossover study design, with treatments separated by a minimum 2-day washout period. Blood samples were collected at various points for measurement of plasma levofloxacin concentration via high-pressure liquid chromatography. Pharmacokinetic analysis was performed with compartmental modeling. RESULTS After oral administration of the levofloxacin tablet, mean (coefficient of variation) peak plasma concentration was 15.5 μg/mL (23.8%), mean elimination half-life was 5.84 hours (20.0%), and mean bioavailability was 104% (29.0%). After IV administration, mean elimination half-life (coefficient of variation) was 6.23 hours (14.7%), systemic clearance was 145.0 mL/kg/h (22.2%), and volume of distribution was 1.19 L/kg (17.1%). CONCLUSIONS AND CLINICAL RELEVANCE In these dogs, levofloxacin was well absorbed when administered orally, and a dose of approximately 25 mg/kg was sufficient to reach pharmacokinetic-pharmacodynamic targets for treating infections with susceptible Enterobacteriaceae (ie, ≤ 0.5 μg/mL) or Pseudomonas aeruginosa (ie, ≤ 1 μg/mL) according to clinical breakpoints established by the Clinical and Laboratory Standards Institute.}, number={10}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Madsen, Melanie and Messenger, Kristen and Papich, Mark G.}, year={2019}, month={Oct}, pages={957–962} }
 @article{bennett_seddighi_moorhead_messenger_cox_sun_pasloske_doherty_2018, title={Effect of fentanyl on the induction dose and minimum infusion rate of alfaxalone preventing movement in female dogs}, volume={45}, ISSN={1467-2987}, url={http://dx.doi.org/10.1016/J.VAA.2018.09.008}, DOI={10.1016/J.VAA.2018.09.008}, abstractNote={Introduction: The study determined the effect of fentanyl on the induction dose and minimum infusion rate of alfaxalone required to prevent movement in response to a noxious stimulus (MIRNM) in dogs.}, number={6}, journal={Veterinary Anaesthesia and Analgesia}, publisher={Elsevier BV}, author={Bennett, Katherine and Seddighi, Reza and Moorhead, Kaitlin and Messenger, Kristen and Cox, Sherry and Sun, Xiaocun and Pasloske, Kirby and Doherty, Thomas}, year={2018}, month={Nov}, pages={885.e2} }
 @article{gulledge_messenger_cornell_lindell_schmiedt_2018, title={Pharmacokinetic comparison of two buprenorphine formulations after buccal administration in healthy male cats}, volume={20}, ISSN={["1532-2750"]}, DOI={10.1177/1098612x17710843}, abstractNote={Objectives The objective of this study was to compare the pharmacokinetics of compounded and commercially available aqueous formulations of buprenorphine after a single buccal dose to healthy cats and to evaluate the concentrations of a compounded buprenorphine solution over 21 days when stored at room temperature (RT; 22-24°C) with exposure to light or when refrigerated at 4°C while protected from light. Methods Six young healthy male cats were administered single buccal doses of compounded and commercially available formulations of buprenorphine (0.03 mg/kg) using a randomized, blinded, two-period crossover design. Blood samples were obtained over a 24 h period and plasma buprenorphine concentrations were determined using ultra-high-pressure liquid chromatography with mass spectrometry detection. Three batches of the compounded formulation were stored at RT or 4°C and aliquots were evaluated over 21 days for buprenorphine concentration using high-performance liquid chromatography with fluorescence detection. Results Plasma concentrations of buprenorphine were above the limit of quantification up to 6 h in some cats and up to 3 h in all cats. The area under the curve was significantly less for the compounded formulation ( P = 0.004). A significant difference was not detected between formulations for time to maximum concentration ( P = 0.11), maximum concentration ( P = 0.06), half-life ( P = 0.88) and mean residence time ( P = 0.57). Buprenorphine concentration in the compounded formulation was not affected by storage condition or time and remained between 90% and 110% of the target concentration at all time points. Conclusions and relevance A buprenorphine solution prepared from sublingual tablets is absorbed after buccal administration in healthy cats. The extent of absorption is significantly less than that of the commercially available formulation. The compounded solution maintains an acceptable buprenorphine concentration for at least 21 days when stored at RT or refrigerated.}, number={4}, journal={JOURNAL OF FELINE MEDICINE AND SURGERY}, author={Gulledge, Brett M. and Messenger, Kristen M. and Cornell, Karen K. and Lindell, Heather and Schmiedt, Chad W.}, year={2018}, month={Apr}, pages={312–318} }
 @article{oda_messenger_carbajal_posner_gardner_hammer_cerreta_lewbart_bailey_2018, title={Pharmacokinetics and pharmacodynamic effects in koi carp (Cyprinus carpio) following immersion in propofol}, volume={45}, ISSN={["1467-2995"]}, DOI={10.1016/j.vaa.2018.02.005}, abstractNote={Objective To test the hypothesis that plasma propofol concentration (PPC) is associated with anesthetic effect in koi carp administered propofol by immersion. Study design Prospective study. Animals Twenty mature koi carp (mean ± standard deviation, 409.4 ± 83.7 g). Methods Fish were immersed in propofol (5 mg L–1). Physiological variables and induction and recovery times were recorded. In phase I, blood was sampled for PPC immediately following induction and at recovery. In phase II, following induction, fish were maintained with propofol (4 mg L–1) via a recirculating system for 20 minutes. Following established induction, blood was sampled at 1, 10 and 20 minutes. In phase III (n = 19), fish were anesthetized as in phase II with blood sampled nine times in a sparse sampling strategy. Simultaneously, a pharmacodynamics rubric was used to evaluate anesthetic depth. PPC was determined using high performance liquid chromatography with fluorescence detection. Following evaluation of normality, data were analyzed using paired t test or Spearman correlation test (significance was set at p < 0.05). Results In phase I, mean PPCs at induction (20.12 μg mL–1) and recovery (11.62 μg mL–1) were different (p < 0.001). In phase II, only mean PPCs at induction (17.92 μg mL–1) and 10 minutes (21.50 μg mL–1) were different (p = 0.013). In phase III, a correlation between PPCs and the pharmacodynamic rubric scores was found (p < 0.001, r = –0.93). There was no correlation between PPCs and recovery time (p = 0.057, r = 0.433). A two-compartment open model was chosen for the pharmacokinetic model. Absorption rate constant, elimination rate constant and intercompartmental rate constant were 0.48, 0.006 and 0.02 minute–1, respectively. Conclusions and clinical relevance Measurable PPCs were achieved in koi carp anesthetized with propofol by immersion. Anesthetic depth of fish was negatively correlated with PPCs, but recovery time was not.}, number={4}, journal={VETERINARY ANAESTHESIA AND ANALGESIA}, author={Oda, Ayako and Messenger, Kristen M. and Carbajal, Liliana and Posner, Lysa P. and Gardner, Brett R. and Hammer, Scott H. and Cerreta, Anthony J. and Lewbart, Gregory A. and Bailey, Kate M.}, year={2018}, month={Jul}, pages={529–538} }
 @article{barletta_ostenkamp_taylor_quandt_lascelles_messenger_2018, title={The pharmacokinetics and analgesic effects of extended-release buprenorphine administered subcutaneously in healthy dogs}, volume={41}, ISSN={["1365-2885"]}, url={https://dx.doi.org/10.1111/jvp.12497}, DOI={10.1111/jvp.12497}, abstractNote={Buprenorphine is a partial μ agonist opioid used for analgesia in dogs. An extended‐release formulation ( ER ‐buprenorphine) has been shown to provide effective analgesia for 72 hr in rats and mice. Six healthy mongrel dogs were enrolled in a randomized, blinded crossover design to describe and compare the pharmacokinetics and pharmacodynamics of ER ‐buprenorphine administered subcutaneous at 0.2 mg/kg ( ER ‐B) and commercially available buprenorphine for injection intravenously at 0.02 mg/kg ( IV ‐B). After drug administration, serial blood samples were collected to measure plasma buprenorphine concentrations using liquid chromatography/mass spectrometry detection. Heart rate, respiratory rate, body temperature, sedation score, and thermal threshold latency were recorded throughout the study. Median (range) terminal half‐life, time to maximum concentration, and maximum plasma concentration of ER ‐buprenorphine were 12.74 hr (10.43–18.84 hr), 8 hr (4–36 hr), and 5.00 ng/ml (4.29–10.98 ng/ml), respectively. Mild bradycardia, hypothermia, and inappetence were noted in both groups. Thermal threshold latency was significantly prolonged compared to baseline up to 12 hr and up to 72 hr in IV ‐B and ER ‐B, respectively. These results showed that ER ‐buprenorphine administered at a dose of 0.2 mg/kg resulted in prolonged and sustained plasma concentrations and antinociceptive effects up to 72 hr after drug administration.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, publisher={Wiley Online Library}, author={Barletta, M. and Ostenkamp, S. M. and Taylor, A. C. and Quandt, J. and Lascelles, B. D. X. and Messenger, K. M.}, year={2018}, month={Aug}, pages={502–512} }
 @article{pastina_early_bergman_nettifee_maller_bray_waldron_castel_munana_papich_et al._2018, title={The pharmacokinetics of cytarabine administered subcutaneously, combined with prednisone, in dogs with meningoencephalomyelitis of unknown etiology}, volume={41}, ISSN={["1365-2885"]}, url={https://doi.org/10.1111/jvp.12667}, DOI={10.1111/jvp.12667}, abstractNote={Abstract The objective of this study was to describe the pharmacokinetics (PK) of cytarabine (CA) after subcutaneous (SC) administration to dogs with meningoencephalomyelitis of unknown etiology (MUE). Twelve dogs received a single SC dose of CA at 50 mg/m 2 as part of treatment of MUE. A sparse sampling technique was used to collect four blood samples from each dog from 0 to 360 min after administration. All dogs were concurrently receiving prednisone (0.5–2 mg kg −1 day −1 ). Plasma CA concentrations were measured by HPLC, and pharmacokinetic parameters were estimated using nonlinear mixed‐effects modeling (NLME). Plasma drug concentrations ranged from 0.05 to 2.8 μg/ml. The population estimate (CV%) for elimination half‐life and Tmax of cytarabine in dogs was 1.09 (21.93) hr and 0.55 (51.03) hr, respectively. The volume of distribution per fraction absorbed was 976.31 (10.85%) ml/kg. Mean plasma concentration of CA for all dogs was above 1.0 μg/ml at the 30‐, 60‐, 90‐, and 120‐min time points. In this study, the pharmacokinetics of CA in dogs with MUE after a single 50 mg/m 2 SC injection in dogs was similar to what has been previously reported in healthy beagles; there was moderate variability in the population estimates in this clinical population of dogs.}, number={5}, journal={Journal of Veterinary Pharmacology & Therapeutics}, publisher={Wiley}, author={Pastina, B. and Early, P.J. and Bergman, R.L. and Nettifee, J. and Maller, A. and Bray, K.Y. and Waldron, R.J. and Castel, A.M. and Munana, K.R. and Papich, M.G. and et al.}, year={2018}, month={Oct}, pages={638–643} }
 @article{barletta_messenger_hofmeister_quandt_2017, title={Determination of MACBAR of sevoflurane and evaluation of the effects of a ketamine constant rate infusion on sevoflurane MACBAR in sheep}, volume={44}, ISSN={1467-2987}, url={http://dx.doi.org/10.1016/J.VAA.2016.12.035}, DOI={10.1016/J.VAA.2016.12.035}, abstractNote={Introduction: Minimizing sympathetic stimulation under general anesthesia prevents activation of the neuroendocrine stress response. The minimum alveolar concentration that blunts adrenergic responses (MACBAR) of sevoflurane in sheep has not been investigated.}, number={1}, journal={Veterinary Anaesthesia and Analgesia}, publisher={Elsevier BV}, author={Barletta, M. and Messenger, K. and Hofmeister, E. and Quandt, J.}, year={2017}, month={Jan}, pages={195.e3} }
 @article{barletta_messenger_smith_thoresen_peroni_quandt_2017, title={Evaluation of cardiovascular variables in sheep anesthetized with sevoflurane in combination with ketamine CRI}, volume={44}, ISSN={1467-2987}, url={http://dx.doi.org/10.1016/J.VAA.2017.09.024}, DOI={10.1016/J.VAA.2017.09.024}, abstractNote={Introduction: Ketamine is often used as a constant rate infusion (CRI) during general anesthesia for its anesthetic sparing effects, analgesia, and cardiovascular support via sympathetic stimulation.}, number={5}, journal={Veterinary Anaesthesia and Analgesia}, publisher={Elsevier BV}, author={Barletta, M. and Messenger, K. and Smith, M. and Thoresen, M. and Peroni, J. and Quandt, J.}, year={2017}, month={Sep}, pages={1262.e11–1262.e12} }
 @article{gruen_messenger_thomson_griffith_aldrich_vaden_lascelles_2017, title={Evaluation of serum cytokines in cats with and without degenerative joint disease and associated pain}, volume={183}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/J.VETIMM.2016.12.007}, DOI={10.1016/J.VETIMM.2016.12.007}, abstractNote={Degenerative joint disease is common in cats, with signs of pain frequently found on orthopedic examination and radiographs often showing evidence of disease. However, understanding of the pathophysiology of degenerative joint disease and associated pain remains limited. Several cytokines have been identified as having a role in pain in humans, but this has not been investigated in cats. The present study was performed to use a multiplex platform to evaluate the concentration of 19 cytokines and chemokines in serum samples obtained from cats with and without degenerative joint disease and associated pain. Samples from a total of 186 cats were analyzed, with cats representing a range of severity on radiographic and orthopedic evaluations and categorized by degenerative joint disease scores and pain scores. Results showed that cats with higher radiographic degenerative joint disease scores have higher serum concentrations of IL-4 and IL-8, while cats with higher orthopedic exam pain scores have higher concentrations of IL-8, IL-2, and TNF-α; increased concentration of IL-8 in degenerative joint disease and pain may be confounded by the association with age. Discriminant analysis was unable to identify one or more cytokines that distinguish between groups of cats classified based on degenerative joint disease score category or pain score category. Finally, cluster analysis driven by analyte concentrations shows separation of groups of cats, but features defining the groups remain unknown. Further studies are warranted to investigate any changes in cytokine concentrations in response to analgesic therapies, and further evaluate the elevations in cytokine concentrations found here, particularly focused on studies of local cytokines present in synovial fluid.}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Gruen, Margaret E. and Messenger, Kristen M. and Thomson, Andrea E. and Griffith, Emily H. and Aldrich, Lauren A. and Vaden, Shelly and Lascelles, B.Duncan X.}, year={2017}, month={Jan}, pages={49–59} }
 @inbook{papich_messenger_2017, title={Non-Steroidal Anti-Inflammatory Drugs}, ISBN={9781119421375 9781118526231}, url={http://dx.doi.org/10.1002/9781119421375.ch12}, DOI={10.1002/9781119421375.ch12}, abstractNote={Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most important drugs used in all species of animals. They possess both analgesic and anti-inflammatory properties. Pharmacokinetic parameter estimates for NSAIDs can be examined using the available data from research reports and the drug package inserts. Among the adverse reactions caused by NSAIDs, gastrointestinal problems are the most frequent reason to discontinue NSAID therapy or consider alternative treatment. In the kidney, prostaglandins play an important role in modulating the tone of blood vessels and regulating salt and water balance. Non-steroidal anti-inflammatory drugs which inhibit COX-1 can reduce thromboxane (TXA2) synthesis in platelets and decrease platelet function. Flunixin meglumine is the most commonly utilized injectable NSAID for acute soft tissue injury, endotoxemia, and abdominal pain. There are veterinary generic formulations of popular drugs and there are some human-labeled drugs that are used off label (e.g., aspirin, naproxen, and piroxicam).}, booktitle={Veterinary Anesthesia and Analgesia}, publisher={John Wiley & Sons, Ltd}, author={Papich, Mark G. and Messenger, Kristin}, year={2017}, month={Apr}, pages={227–243} }
 @article{williams_long_durrant_mckeon_shive_griffith_messenger_fish_2017, title={Oral transmucosal detomidine gel in New Zealand white rabbits (Oryctolagus cuniculus)}, volume={56}, number={4}, journal={Journal of the American Association for Laboratory Animal Science}, author={Williams, M. D. and Long, C. T. and Durrant, J. R. and McKeon, G. P. and Shive, H. R. and Griffith, E. H. and Messenger, K. M. and Fish, R. E.}, year={2017}, pages={436–442} }
 @article{ostenkamp_barletta_quandt_lascelles_messenger_2017, title={Pharmacokinetics and pharmacodynamics of an extended-release buprenorphine formulation in dogs}, volume={44}, ISSN={1467-2987}, url={http://dx.doi.org/10.1016/J.VAA.2016.12.042}, DOI={10.1016/J.VAA.2016.12.042}, abstractNote={Introduction: Options for effective and safe long-term analgesia in dogs are limited. The purpose of this study was to describe the pharmacokinetics and pharmacodynamics of an extended-release buprenorphine (ER-B) formulation in healthy dogs.}, number={1}, journal={Veterinary Anaesthesia and Analgesia}, publisher={Elsevier BV}, author={Ostenkamp, S. and Barletta, M. and Quandt, J. and Lascelles, D. and Messenger, K.}, year={2017}, month={Jan}, pages={195.e6} }
 @article{smith_messenger_gould_knych_tolbert_2017, title={Pharmacokinetics, sedation, and hemodynamic changes following administration of oral transmucosal detomidine gel in cats}, volume={44}, ISSN={1467-2987}, url={http://dx.doi.org/10.1016/J.VAA.2016.12.040}, DOI={10.1016/J.VAA.2016.12.040}, abstractNote={Introduction: The objective of this study was to describe the pharmacokinetics of oral transmuscosal (OTM) detomidine gel in healthy cats, and assess its effects on sedation and hemodynamic variables, in order to investigate this noninvasive route of sedative administration.}, number={1}, journal={Veterinary Anaesthesia and Analgesia}, publisher={Elsevier BV}, author={Smith, P. and Messenger, K. and Gould, E. and Knych, H. and Tolbert, M.}, year={2017}, month={Jan}, pages={195.e5–195.e6} }
 @article{early_crook_williams_davis_munana_papich_messenger_2017, title={Plasma and serum concentrations of cytarabine administered via continuous intravenous infusion to dogs with meningoencephalomyelitis of unknown etiology}, volume={40}, ISSN={["1365-2885"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84988369300&partnerID=MN8TOARS}, DOI={10.1111/jvp.12360}, abstractNote={The objective of this study was to evaluate the plasma and serum concentrations of cytarabine (CA) administered via constant rate infusion (CRI) in dogs with meningoencephalomyelitis of unknown etiology (MUE). Nineteen client-owned dogs received a CRI of CA at a dose of 25 mg/m2 /h for 8 h as treatment for MUE. Dogs were divided into four groups, those receiving CA alone and those receiving CA in conjunction with other drugs. Blood samples were collected at 0, 1, 8, and 12 h after initiating the CRI. Plasma (n = 13) and serum (n = 11) cytarabine concentrations were measured by high-pressure liquid chromatography. The mean peak concentration (CMAX ) and area under the curve (AUC) after CRI administration were 1.70 ± 0.66 μg/mL and 11.39 ± 3.37 h·μg/mL, respectively, for dogs receiving cytarabine alone, 2.36 ± 0.35 μg/mL and 16.91 + 3.60 h·μg/mL for dogs administered cytarabine and concurrently on other drugs. Mean concentrations for all dogs were above 1.0 μg/mL at both the 1- and 8-h time points. The steady-state achieved with cytarabine CRI produces a consistent and prolonged exposure in plasma and serum, which is likely to produce equilibrium between blood and the central nervous system in dogs with a clinical diagnosis of MUE. Other medications commonly used to treat MUE do not appear to alter CA concentrations in serum and plasma.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Early, P. J. and Crook, K. I. and Williams, L. M. and Davis, E. G. and Munana, K. R. and Papich, M. G. and Messenger, K. M.}, year={2017}, month={Aug}, pages={411–414} }
 @article{oda_messenger_carbajal_gardner_hammer_cerreta_lewbart_posner_bailey_2017, title={Plasma propofol concentrations and pharmacodynamic effects in koi carp ( Cyprinus carpio ) following exposure via immersion}, volume={44}, ISSN={1467-2987}, url={http://dx.doi.org/10.1016/J.VAA.2017.09.009}, DOI={10.1016/J.VAA.2017.09.009}, abstractNote={Introduction: This study was performed to determine the association between plasma propofol concentration (PPC) and anesthetic effect in koi carp anesthetized with propofol via immersion.}, number={5}, journal={Veterinary Anaesthesia and Analgesia}, publisher={Elsevier BV}, author={Oda, A. and Messenger, K. and Carbajal, L. and Gardner, B. and Hammer, S. and Cerreta, A. and Lewbart, G. and Posner, L. and Bailey, K.}, year={2017}, month={Sep}, pages={1262.e4–1262.e5} }
 @article{gruen_messenger_thomson_griffith_paradise_vaden_lascelles_2016, title={A comparison of serum and plasma cytokine values using a multiplexed assay in cats}, volume={182}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2016.10.003}, DOI={10.1016/j.vetimm.2016.10.003}, abstractNote={Degenerative joint disease (DJD) is highly prevalent in cats, and pain contributes to morbidity. In humans, alterations of cytokine concentrations have been associated with joint deterioration and pain. Similar changes have not been investigated in cats. Cytokine concentrations can be measured using multiplex technology with small samples of serum or plasma, however, serum and plasma are not interchangeable for most bioassays. Correlations for cytokine concentrations between serum and plasma have not been evaluated in cats.To evaluate the levels of detection and agreement between serum and plasma samples in cats.Paired serum and plasma samples obtained from 38 cats.Blood was collected into anti-coagulant free and EDTA Vacutainer® tubes, serum or plasma extracted, and samples frozen at -80°C until testing. Duplicate samples were tested using a 19-plex feline cytokine/chemokine magnetic bead panel.Agreement between serum and plasma for many analytes was high, however correlation coefficients ranged from -0.01 to 0.97. Results from >50% of samples were below the lower limit of quantification for both serum and plasma for nine analytes, and for an additional three analytes for plasma only.While serum and plasma agreement was generally good, detection was improved using serum samples.}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Gruen, Margaret E. and Messenger, Kristen M. and Thomson, Andrea E. and Griffith, Emily H. and Paradise, Hayley and Vaden, Shelly and Lascelles, B.D.X.}, year={2016}, month={Dec}, pages={69–73} }
 @article{risselada_marcellin-little_messenger_griffith_davidson_papich_2016, title={Assessment of in vitro release of carboplatin from six carrier media}, volume={77}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.77.12.1381}, abstractNote={OBJECTIVE To investigate in vitro carboplatin release from 6 carrier media. SAMPLE 6 carboplatin-containing carrier media. PROCEDURES An in vitro release study was performed with 6 commercially available carrier media: a hemostatic gelatin sponge, a poloxamer copolymer gel, and 2 sizes (3 and 4.8 mm in diameter) of beads molded from each of 2 commercial calcium sulfate products. All carrier media contained 10 mg of carboplatin. Carrier media specimens were placed in 37°C PBS solution for 96 hours. Carboplatin concentrations in PBS solution were measured by use of high-performance liquid chromatography at 15 time points to calculate the amount and proportion of carboplatin released from each specimen. RESULTS Peak release of carboplatin from the poloxamer copolymer gel and hemostatic gelatin sponge were achieved after 4 and 20 hours, respectively. Maximum release did not differ significantly between the poloxamer copolymer gel and hemostatic gelatin sponge, but both released significantly more carboplatin within 96 hours than did both of the commercial calcium sulfate products. The poloxamer copolymer gel released 99% of the carboplatin, and the hemostatic gelatin sponge released 68.5% of the carboplatin. Peak release of carboplatin from the calcium sulfate beads was not reached within 96 hours. CONCLUSIONS AND CLINICAL RELEVANCE In this study, carboplatin release from the hemostatic gelatin sponge was incomplete. The poloxamer copolymer gel and hemostatic gelatin sponge released carboplatin rapidly in vitro, whereas calcium sulfate beads did not.}, number={12}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Risselada, Marije and Marcellin-Little, Denis J. and Messenger, Kristen M. and Griffith, Emily and Davidson, Gigi S. and Papich, Mark G.}, year={2016}, month={Dec}, pages={1381–1386} }
 @article{messenger_wofford_papich_2016, title={Carprofen pharmacokinetics in plasma and in control and inflamed canine tissue fluid using in vivo ultrafiltration}, volume={39}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.12233}, abstractNote={Measurement of unbound drug concentrations at their sites of action is necessary for accurate PK / PD modeling. The objective of this study was to determine the unbound concentration of carprofen in canine interstitial fluid ( ISF ) using in vivo ultrafiltration and to compare pharmacokinetic parameters of free carprofen concentrations between inflamed and control tissue sites. We hypothesized that active concentrations of carprofen would exhibit different dispositions in ISF between inflamed vs. normal tissues. Bilateral ultrafiltration probes were placed subcutaneously in six healthy B eagle dogs 12 h prior to induction of inflammation. Two milliliters of either 2% carrageenan or saline control was injected subcutaneously at each probe site, 12 h prior to intravenous carprofen (4 mg/kg) administration. Plasma and ISF samples were collected at regular intervals for 72 h, and carprofen concentrations were determined using HPLC . Prostaglandin E 2 ( PGE 2 ) concentrations were quantified in ISF using ELISA . Unbound carprofen concentrations were higher in ISF compared with predicted unbound plasma drug concentrations. Concentrations were not significantly higher in inflamed ISF compared with control ISF . Compartmental modeling was used to generate pharmacokinetic parameter estimates, which were not significantly different between sites. Terminal half‐life ( T ½) was longer in the ISF compared with plasma. PGE 2 in ISF decreased following administration of carprofen. In vivo ultrafiltration is a reliable method to determine unbound carprofen in ISF , and that disposition of unbound drug into tissue is much higher than predicted from unbound drug concentration in plasma. However, concentrations and pharmacokinetic parameter estimates are not significantly different in inflamed vs. un‐inflamed tissues.}, number={1}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Messenger, K. M. and Wofford, J. A. and Papich, M. G.}, year={2016}, month={Feb}, pages={32–39} }
 @article{curto_messenger_salmon_gilger_2016, title={Cytokine and chemokine profiles of aqueous humor and serum in horses with uveitis measured using multiplex bead immunoassay analysis}, volume={182}, ISSN={["1873-2534"]}, url={https://doi.org/10.1016/j.vetimm.2016.09.008}, DOI={10.1016/j.vetimm.2016.09.008}, abstractNote={To determine whether horses with clinically diagnosed Equine Recurrent Uveitis (ERU) and those with Leptospirosis infection have a specific cytokine profile in their aqueous humor (AH) and serum that differs from horses with uveitis secondary to other ocular inflammatory processes and from horses with normal eyes.Twenty-five client-owned horses with uveitis that were presented to the North Carolina State University Ophthalmology Service, and four University-owned horses without history or clinical signs of ocular disease.Samples of AH and serum were obtained from horses with ERU (n=13), acute or non-recurrent uveitis (UV; n=7), uveitis secondary to infectious keratitis (IK; n=5), and normal eyes (N; n=4). Cytokine levels in AH and serum were quantified using a multiplex bead immunoassay. Leptospiral antibody titers in serum and AH and PCR for Leptospiral DNA in AH were performed.In the AH of horses with ERU, increased levels of IL-1a, IL-4, IL-6, IL-8, IL-12p70, FGF-2, G-CSF, and RANTES were measured compared to UV, IK and N eyes, but the differences were not significant. However, IL-10 was significantly higher in ERU eyes compared to IK and N (P=0.029; 0.013), and IP-10 in ERU eyes was significantly higher than in UV and N (P=0.004). Furthermore, MCP-1 was significantly higher in ERU than N (P=0.04). In the serum, increased levels of IL-1a, IL-4, IL-6, IL-8, IL-12p70, fractalkine, and G-CSF were measured in horses with ERU, but the levels were not significantly higher than those observed in UV, IK, or N horses. However, serum IP-10 levels in horses with ERU were significantly higher than in UV and N horses (P=0.005) and MCP-1 levels were significantly higher in ERU than N (P=0.03). Horses with marked ocular inflammation had significantly higher serum levels of G-CSF, IL-1a, fractalkine, IL-13, IL-4, IL-17a, IL-12p70, IFN-γ, and MCP-1. Elevated IL-10 in AH was significantly associated with disease chronicity, both overall and in ERU eyes (P=0.049), and in horses with positive ocular leptospiral titers or leptospiral PCR, significant elevations of IL-10 (P=0.0018; 0.0032) and IP-10 (P=0.0342; 0.043) were detected in the AH compared to leptospiral negative eyes.The anti-inflammatory cytokine IL-10 and the pro-inflammatory cytokine IP-10 appear to play an important role in ERU. Further studies are needed to further clarify and characterize cytokine profiles of specific ocular inflammatory diseases, but multiplex bead immunoassay technology shows promise as a diagnostically valuable tool.}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, publisher={Elsevier BV}, author={Curto, Elizabeth and Messenger, Kristen M. and Salmon, Jacklyn H. and Gilger, Brian C.}, year={2016}, month={Dec}, pages={43–51} }
 @article{messenger_hopfensperger_knych_papich_2016, title={Pharmacokinetics of detomidine following intravenous or oral-transmucosal administration and sedative effects of the oral-transmucosal treatment in dogs}, volume={77}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.77.4.413}, abstractNote={Abstract OBJECTIVE To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs. ANIMALS 12 healthy adult dogs. PROCEDURES In phase 1, detomidine was administered by IV (0.5 mg/m 2 ) or OTM (1 mg/m 2 ) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m 2 ) or detomidine gel by OTM administration (0.5 mg/m 2 ), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment. RESULTS Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation. CONCLUSIONS AND CLINICAL RELEVANCE Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.}, number={4}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Messenger, Kristen M. and Hopfensperger, Marie and Knych, Heather K. and Papich, Mark G.}, year={2016}, month={Apr}, pages={413–420} }
 @inbook{jarrett_bailey_messenger_prange_gaines_posner_2016, title={Recovery of horses from general anesthesia following induction with either propofol or midazolam followed by ketamine}, volume={253}, DOI={10.2460/javma.253.1.101}, abstractNote={OBJECTIVE To evaluate quality of recovery from general anesthesia in horses after induction with propofol and ketamine versus midazolam and ketamine. DESIGN Prospective randomized crossover study. ANIMALS 6 healthy adult horses. PROCEDURES Horses were premedicated with xylazine (1.0 mg/kg [0.45 mg/lb], IV), and general anesthesia was induced with midazolam (0.1 mg/kg [0.045 mg/lb], IV) or propofol (0.5 mg/kg [0.23 mg/lb], IV), followed by ketamine (3.0 mg/kg [1.36 mg/lb], IV). Horses were endotracheally intubated, and anesthesia was maintained with isoflurane. After 60 minutes, horses were given romifidine (0.02 mg/kg [0.009 mg/lb], IV) and allowed to recover unassisted. Times to first movement, sternal recumbency, and standing and the number of attempts to stand were recorded. Plasma concentrations of propofol or midazolam were measured following induction and immediately before recovery. Recovery quality was scored by 3 graders with a recovery rubric and a visual analog scale. RESULTS Number of attempts to stand was significantly lower when horses received propofol (median, 2; range, 1 to 3) than when they received midazolam (median, 7.5; range, 3 to 16). For both the recovery rubric and visual analog scale, recovery quality was significantly better when horses received propofol than when they received midazolam. Plasma drug concentration at recovery, as a percentage of the concentration at induction, was significantly lower when horses received propofol than when they received midazolam. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that for horses undergoing short (ie, 60 minutes) periods of general anesthesia, recovery quality may be better following induction with propofol and ketamine, compared with midazolam and ketamine.}, number={1}, booktitle={Journal of the American Veterinary Medical Association}, author={Jarrett, M.A. and Bailey, K.M. and Messenger, K.M. and Prange, T. and Gaines, B. and Posner, L.P.}, year={2016}, month={Jul}, pages={101–107} }
 @article{parkinson_tolbert_messenger_odunayo_brand_davidson_peters_reed_papich_2015, title={Evaluation of the Effect of Orally Administered Acid Suppressants on Intragastric pH in Cats}, volume={29}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.12493}, abstractNote={Background Acid suppressant drugs are a mainstay of treatment for cats with gastrointestinal erosion and ulceration. However, clinical studies have not been performed to compare the efficacy of commonly PO administered acid suppressants in cats. Hypothesis/Objectives To compare the effect of PO administered famotidine, fractionated omeprazole tablet ( fOT ), and omeprazole reformulated paste (ORP) on intragastric pH in cats. We hypothesized that both omeprazole formulations would be superior to famotidine and placebo. Animals Six healthy adult DSH colony cats. Methods Utilizing a randomized, 4‐way crossover design, cats received 0.88–1.26 mg/kg PO q12h fOT , ORP, famotidine, and placebo (lactose capsules). Intragastric pH monitoring was used to continuously record intragastric pH for 96 hours beginning on day 4 of treatment. Plasma omeprazole concentrations at steady state (day 7) were determined by high performance liquid chromatography (HPLC) with ultraviolet detection. Mean percentage time that intragastric pH was ≥3 and ≥4 were compared among groups using ANOVA with a posthoc Tukey‐Kramer test (α = 0.05). Results The mean percentage time ± SD that intragastric pH was ≥3 was 68.4 ± 35.0% for fOT , 73.9 ± 23.2% for ORP, 42.8 ± 18.6% for famotidine, and 16.0 ± 14.2% for placebo. Mean ± SD plasma omeprazole concentrations were similar in cats receiving fOT compared to those receiving ORP and in a range associated with acid suppression reported in other studies. Conclusions and Clinical Importance These results suggest that both omeprazole formulations provide superior acid suppression in cats compared to famotidine or placebo. Fractionated enteric‐coated OT is an effective acid suppressant despite disruption of the enteric coating.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Parkinson, S. and Tolbert, K. and Messenger, K. and Odunayo, A. and Brand, M. and Davidson, G. and Peters, E. and Reed, A. and Papich, M. G.}, year={2015}, pages={104–112} }
 @article{phillips_harms_messenger_2015, title={Oral Transmucosal Detomidine Gel for the Sedation of the Domestic Ferret (Mustela putorius furo)}, volume={24}, ISSN={1557-5063}, url={http://dx.doi.org/10.1053/j.jepm.2015.08.012}, DOI={10.1053/j.jepm.2015.08.012}, abstractNote={The restraint of ferrets for physical examination and venipuncture often employs chemical means with parenteral drug injection or inhalant anesthetics. These methods often result in agitation, pain at the injection site, increased stress, and increased cost. A transmucosal (TM) detomidine gel has recently been evaluated for sedation to facilitate physical examination and common procedures in dogs and horses. The purpose of the present study was to evaluate TM detomidine in the domestic ferret for physical examination and venipuncture in a teaching laboratory setting. Detomidine was evaluated at 2 doses: 2 and 4 mg/m2. A total of 16 ferrets (8 female and 8 male) were randomly assigned to each dose group. Following the administration of detomidine, physiologic variables were collected (heart rate, respiratory rate, and rectal temperature) and sedation scoring was performed every 10 minutes. Owing to the rapid effect of the drug, time of onset was not consistently captured in the data recording protocol; the 8 males were used again in a subsequent laboratory and dosed at 3 mg/m2 to refine the times of initial effect and dorsal recumbency. Venipuncture was attempted only after full physical examinations were completed and the ferrets could be placed in dorsal recumbency. Venipuncture was performed with detomidine sedation alone on 4 female and 5 male ferrets, with no significant difference based on dose group. Isoflurane was administered via face mask to the remaining ferrets due to insufficient sedation based on muscle movement and reaction to venipuncture. Heart rate significantly decreased following detomidine administration as compared with baseline values in both dose groups. There were no significant changes in respiratory rates. Sedation scores were significantly increased throughout the study period. Side effects of detomidine administration included piloerection of the tail in all ferrets and a second-degree atrioventricular block in one female ferret that resolved following reversal with atipamezole. Hyperglycemia was observed in 67% of the ferrets. TM detomidine effectively sedated domestic ferrets for physical examination and venipuncture.}, number={4}, journal={Journal of Exotic Pet Medicine}, publisher={Elsevier BV}, author={Phillips, Brianne E. and Harms, Craig A. and Messenger, Kristen M.}, year={2015}, month={Oct}, pages={446–454} }
 @article{chinnadurai_messenger_papich_harms_2014, title={Meloxicam pharmacokinetics using nonlinear mixed-effects modeling in ferrets after single subcutaneous administration}, volume={37}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/jvp.12099}, DOI={10.1111/jvp.12099}, abstractNote={This study was designed to investigate the pharmacokinetics of meloxicam, an oxicam class, nonsteroidal anti‐inflammatory drug ( NSAID ), in ferrets. We determined the pharmacokinetic properties of a single subcutaneous dose of meloxicam (0.2 mg/kg) in nine male and nine female ferrets. Blood samples were collected by venipuncture of the cranial vena cava into heparinized syringes. Plasma meloxicam concentrations were determined by high‐pressure liquid chromatography ( HPLC ). Pharmacokinetic variables were calculated using nonlinear mixed‐effects modeling to take advantage of the population‐based sampling scheme and to minimize sample volume collected per animal. Maximum plasma concentration, volume of distribution per absorption, and elimination half‐life were 0.663 μ g/mL, 0.21 L, and 11.4 h, respectively, for females and 0.920 μ g/mL, 0.35 L, and 17.8 h, respectively, for males. Significant differences were found in each of the above parameters between male and female ferrets. Systemic clearance per absorption was not affected by gender and was 13.4 mL/h. Analgesic efficacy was not evaluated, but plasma meloxicam concentrations achieved in these animals are considered effective in other species. Sex differences in the pharmacokinetic behavior of meloxicam should be taken into consideration when treating ferrets.}, number={4}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Chinnadurai, S. K. and Messenger, K. M. and Papich, M. G. and Harms, C. A.}, year={2014}, month={Feb}, pages={382–387} }
 @article{hutchins_messenger_vaden_2013, title={Suspected carprofen toxicosis caused by coprophagia in a dog}, volume={243}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.243.5.709}, DOI={10.2460/javma.243.5.709}, abstractNote={Abstract Case Description —A 1-year-old spayed female mixed-breed dog was evaluated because of urinary incontinence, polyuria, polydipsia, and minimally concentrated urine. Clinical Findings —Markedly high circulating alanine transaminase activity, mildly high circulating alkaline phosphatase activity, and low urine specific gravity were detected for the dog. Results of ultrasonographic examination of the abdomen and cytologic examination of liver samples were unremarkable. Carprofen was detected in serum and plasma samples obtained from the dog. Exposure to carprofen was attributed to ingestion of feces of another dog in the household that was receiving the drug daily. Treatment and Outcome —Access to feces of other dogs in the household was prevented; no other treatment was initiated. Urinary incontinence, polyuria, and polydipsia resolved, and urine specific gravity increased within 7 days following discontinuation of consumption of feces. Alanine transaminase activity was substantially lower than the value determined during the initial examination, and alkaline phosphatase activity was within the reference range 5 weeks after discontinuation of consumption of feces by the dog. Clinical Relevance —Findings for the dog of this report suggested that carprofen toxicosis can be caused by consumption of feces of another dog receiving the drug. This cause of adverse effects should be a differential diagnosis for dogs with clinical signs and clinicopathologic abnormalities consistent with carprofen toxicosis.}, number={5}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Hutchins, Rae G. and Messenger, Kristen M. and Vaden, Shelly L.}, year={2013}, month={Sep}, pages={709–711} }
 @article{crook_early_messenger_munana_gallagher_papich_2013, title={The pharmacokinetics of cytarabine in dogs when administered via subcutaneous and continuous intravenous infusion routes}, volume={36}, ISSN={["1365-2885"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84880035701&partnerID=MN8TOARS}, DOI={10.1111/jvp.12008}, abstractNote={This crossover study compared the pharmacokinetics of cytarabine in six healthy dogs following intravenous constant rate infusion (CRI) and subcutaneous (SC) administrations, as these are two routes of administration commonly employed in the treatment of meningoencephalitis of unknown etiology. Each dog received a SC cytarabine injection of 50 mg/m(2) or an 8 h CRI of 25 mg/m(2) per hour, with a 7-day washout before receiving the alternative treatment. Blood samples were collected for 16 h after CRI initiation and for 8 h after SC injection. Plasma concentrations were measured by high-pressure liquid chromatography (HPLC). Pharmacokinetic parameters were estimated using the best-fit compartmental analysis for both CRI and SC routes. Terminal half-life (T(1/2) ) of cytarabine was 1.35 ± 0.3 and 1.15 ± 0.13 h after SC administration and CRI, respectively. Mean peak concentration (Cmax ) was 2.88 and 2.80 μg/mL for SC and CRI administration, respectively. Volume of distribution was 0.66 ± 0.07 l/kg. The 8-h CRI produced steady-state plasma concentrations as determined by consecutive measurement that did not decline until the end of the infusion. The SC administration did not achieve steady-state concentrations because cytarabine administered by this route was rapidly absorbed and eliminated quickly. The steady state achieved with the cytarabine CRI may produce a more prolonged exposure of cytarabine at cytotoxic levels in plasma compared to the concentrations after SC administration.}, number={4}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Crook, K. I. and Early, P. J. and Messenger, K. M. and Munana, K. R. and Gallagher, R. and Papich, M. G.}, year={2013}, month={Aug}, pages={408–411} }
 @article{schwartz_munana_nettifee-osborne_messenger_papich_2013, title={The pharmacokinetics of midazolam after intravenous, intramuscular, and rectal administration in healthy dogs}, volume={36}, ISSN={["0140-7783"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84883647308&partnerID=MN8TOARS}, DOI={10.1111/jvp.12032}, abstractNote={Intravenous benzodiazepines are utilized as first‐line drugs to treat prolonged epileptic seizures in dogs and alternative routes of administration are required when venous access is limited. This study compared the pharmacokinetics of midazolam after intravenous (IV), intramuscular (IM), and rectal (PR) administration. Six healthy dogs were administered 0.2 mg/kg midazolam IV, IM, or PR in a randomized, 3‐way crossover design with a 3‐day washout between study periods. Blood samples were collected at baseline and at predetermined intervals until 480 min after administration. Plasma midazolam concentrations were measured by high‐pressure liquid chromatography with UV detection. Rectal administration resulted in erratic systemic availability with undetectable to low plasma concentrations. Arithmetic mean values ± SD for midazolam peak plasma concentrations were 0.86 ± 0.36 μg/mL ( C 0 ) and 0.20 ± 0.06 μg/mL ( C max ), following IV and IM administration, respectively. Time to peak concentration ( T max ) after IM administration was 7.8 ± 2.4 min with a bioavailability of 50 ± 16%. Findings suggest that IM midazolam might be useful in treating seizures in dogs when venous access is unavailable, but higher doses may be needed to account for intermediate bioavailability. Rectal administration is likely of limited efficacy for treating seizures in dogs.}, number={5}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Schwartz, M. and Munana, K. R. and Nettifee-Osborne, J. A. and Messenger, K. M. and Papich, M. G.}, year={2013}, month={Oct}, pages={471–477} }
 @article{hopfensperger_messenger_papich_sherman_2013, title={The use of oral transmucosal detomidine hydrochloride gel to facilitate handling in dogs}, volume={8}, ISSN={["1878-7517"]}, DOI={10.1016/j.jveb.2012.10.004}, abstractNote={Safe and humane handling in the veterinary clinic can be challenging when dealing with fearful or anxious dogs. Historically, alpha-2 adrenergic agonists have been used via parenteral routes to facilitate handling of difficult canine subjects. Detomidine hydrochloride is an alpha-2 agonist sedative commercially available in an oral transmucosal (OTM) formulation (Dormosedan Gel; Pfizer Animal Health, Madison, NJ) approved for sedation and restraint in horses. The usefulness of this detomidine formulation has not been previously reported in dogs. This study evaluated the behavioral and physiological effects of OTM detomidine gel administration in dogs to assess its efficacy and safety for facilitation of handling canine subjects. Six healthy institution-owned adult dogs were administered detomidine gel at a dose of 0.35 mg/m2 via OTM route. Behavioral and physiological assessments were performed pretreatment and repeated every 15–30 minutes for 5 hours after administration. Behavioral assessments included global sedation (GS), composite sedation (CS), global anxiolysis (GA), and ease of handling (EH) scores. Physiological assessments included heart rate and rhythm, respiratory rate, mucous membrane color, indirect blood pressure, rectal temperature, oxygen saturation, and capillary refill time. Posttreatment GS, CS, GA, and EH scores were improved for all 6 subjects as compared with pretreatment. For 4 of 6 dogs, maximal GS scores occurred at 45 minutes posttreatment, and duration of maximal GS scores was 30 minutes. Five of 6 dogs achieved adequate GS scores. EH scores were significantly higher during time points of adequate GS scores as compared with time points when adequate GS scores were not achieved. The physiological measures revealed transient bradycardia in 5 of 6 dogs and intermittent second-degree atrioventricular block in 1 dog. No other significant adverse events were noted, and all dogs recovered uneventfully. OTM detomidine gel was safely administered to 6 dogs at a dose of 0.35 mg/m2 and resulted in measurable sedation, anxiolysis, and improved EH in all subjects. Although further evaluation is warranted for use in client-owned dogs, OTM detomidine gel offers a novel sedative and anxiolytic option to facilitate handling of canine subjects.}, number={3}, journal={JOURNAL OF VETERINARY BEHAVIOR-CLINICAL APPLICATIONS AND RESEARCH}, author={Hopfensperger, Marie J. and Messenger, Kristen M. and Papich, Mark G. and Sherman, Barbara L.}, year={2013}, pages={114–123} }
 @article{da cunha_messenger_stout_barker_nevarez_queiroz-williams_tully_2012, title={Pharmacokinetics of lidocaine and its active metabolite monoethylglycinexylidide after a single intravenous administration in chickens (Gallus domesticus) anesthetized with isoflurane}, volume={35}, ISSN={["1365-2885"]}, DOI={10.1111/j.1365-2885.2011.01358.x}, abstractNote={Journal of Veterinary Pharmacology and TherapeuticsVolume 35, Issue 6 p. 604-607 SHORT COMMUNICATION Pharmacokinetics of lidocaine and its active metabolite monoethylglycinexylidide after a single intravenous administration in chickens (Gallus domesticus) anesthetized with isoflurane A. F. DA CUNHA, A. F. DA CUNHA Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this authorK. M. MESSENGER, K. M. MESSENGER Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorR. W. STOUT, R. W. STOUT Department of Laboratory Animal Medicine, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this authorS. A. BARKER, S. A. BARKER Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this authorJ. G. NEVAREZ, J. G. NEVAREZ Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this authorP. QUEIROZ-WILLIAMS, P. QUEIROZ-WILLIAMS Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this authorT. N. TULLY JR, T. N. TULLY JR Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this author A. F. DA CUNHA, A. F. DA CUNHA Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this authorK. M. MESSENGER, K. M. MESSENGER Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, USASearch for more papers by this authorR. W. STOUT, R. W. STOUT Department of Laboratory Animal Medicine, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this authorS. A. BARKER, S. A. BARKER Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this authorJ. G. NEVAREZ, J. G. NEVAREZ Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this authorP. QUEIROZ-WILLIAMS, P. QUEIROZ-WILLIAMS Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this authorT. N. TULLY JR, T. N. TULLY JR Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USASearch for more papers by this author First published: 29 December 2011 https://doi.org/10.1111/j.1365-2885.2011.01358.xCitations: 11 Dr Anderson F. Da Cunha, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA 70803. E-mail: adacunha@vetmed.lsu.edu Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume35, Issue6December 2012Pages 604-607 RelatedInformation}, number={6}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Da Cunha, A. F. and Messenger, K. M. and Stout, R. W. and Barker, S. A. and Nevarez, J. G. and Queiroz-Williams, P. and Tully, T. N., Jr.}, year={2012}, month={Dec}, pages={604–607} }
 @article{messenger_papich_blikslager_2011, title={Distribution of enrofloxacin and its active metabolite, using an in vivo ultrafiltration sampling technique after the injection of enrofloxacin to pigs}, volume={35}, ISSN={0140-7783}, url={http://dx.doi.org/10.1111/j.1365-2885.2011.01338.x}, DOI={10.1111/j.1365-2885.2011.01338.x}, abstractNote={Messenger, K. M., Papich, M. G., Blikslager, A. T. Distribution of enrofloxacin and its active metabolite, using an in vivo ultrafiltration sampling technique after the injection of enrofloxacin to pigs. J. vet. Pharmacol. Therap. 35 , 452–459. The objective of this study was to determine the pharmacokinetics (PK) of enrofloxacin in pigs and compare to the tissue interstitial fluid (ISF). Six healthy, young pigs were administered 7.5 mg/kg enrofloxacin subcutaneously (SC). Blood and ISF samples were collected from preplaced intravenous catheters and ultrafiltration sampling probes placed in three different tissue sites (intramuscular, subcutaneous, and intrapleural). Enrofloxacin concentrations were measured using high‐pressure liquid chromatography with fluorescence detection, PK parameters were analyzed using a one‐compartment model, and protein binding was determined using a microcentrifugation system. Concentrations of the active metabolite ciprofloxacin were negligible. The mean ± SD enrofloxacin plasma half‐life, volume of distribution, clearance, and peak concentration were 26.6 ± 6.2 h (harmonic mean), 6.4 ± 1.2 L/kg, 0.18 ± 0.08 L/kg/h, and 1.1 ± 0.3 μg/mL, respectively. The half‐life of enrofloxacin from the tissues was 23.6 h, and the maximum concentration was 1.26 μg/mL. Tissue penetration, as measured by a ratio of area‐under‐the‐curve (AUC), was 139% (±69%). Plasma protein binding was 31.1% and 37.13% for high and low concentrations, respectively. This study demonstrated that the concentration of biologically active enrofloxacin in tissues exceeds the concentration predicted by the unbound fraction of enrofloxacin in pig plasma. At a dose of 7.5 mg/kg SC, the high tissue concentrations and long half‐life produce an AUC/MIC ratio sufficient for the pathogens that cause respiratory infections in pigs.}, number={5}, journal={Journal of Veterinary Pharmacology and Therapeutics}, publisher={Wiley}, author={Messenger, K. M. and Papich, M. G. and Blikslager, A. T.}, year={2011}, month={Sep}, pages={452–459} }
 @article{messenger_davis_lafevers_barlow_posner_2011, title={Intravenous and sublingual buprenorphine in horses: pharmacokinetics and influence of sampling site}, journal={Veterinary Anaesthesia and Analgesia}, author={Messenger, K.M. and Davis, J.L. and Lafevers, D.H. and Barlow, B.M. and Posner, L.P.}, year={2011}, month={Apr} }
 @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={Davis, J. L., Messenger, K. M., LaFevers, D. H., Barlow, B. M., Posner, L. P. Pharmacokinetics of intravenous and intramuscular buprenorphine in the horse. J. vet. Pharmacol. Therap. 35 , 52–58. 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} }