@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={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{enomoto_love_madsen_wallace_messenger_2022, title={Pharmacokinetics of intravenous, oral transmucosal, and intranasal buprenorphine in healthy male dogs}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.13056}, abstractNote={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{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} }