Pharmacokinetics of pimobendan after oral administration to dogs with myxomatous mitral valve disease.

Autor: McManamey AK; Department of Veterinary Clinical Sciences, Purdue University College of Veterinary Medicine, West Lafayette, Indiana, USA., DeFrancesco TC; Department of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina, USA., Meurs KM; Department of Clinical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina, USA., Papich MG; Department of Molecular Biomedical Sciences, North Carolina State University, College of Veterinary Medicine, Raleigh, North Carolina, USA.
Jazyk: angličtina
Zdroj: Journal of veterinary internal medicine [J Vet Intern Med] 2023 Nov-Dec; Vol. 37 (6), pp. 2003-2010. Date of Electronic Publication: 2023 Sep 30.
DOI: 10.1111/jvim.16891
Abstrakt: Background: Pimobendan is an important therapy for dogs with myxomatous mitral valve disease (MMVD). The pharmacokinetics are reported in healthy dogs but not in dogs with heart disease.
Hypothesis/objectives: To determine if dog characteristics such as age, breed, body condition score, ACVIM stage of heart disease or biochemical laboratory value alter the pharmacokinetics of orally administered pimobendan and its metabolite in a cohort of dogs with naturally occurring MMVD.
Animals: Fifty-seven client-owned dogs with MMVD ACVIM Stage B2, C, or D and administered pimobendan to steady state blood concentrations.
Methods: Prospective, observational study. Samples were collected using a sparse-sampling protocol at specific intervals after administration of pimobendan. Plasma pimobendan and the active metabolite (O-desmethyl-pimobendan, ODMP) concentrations were determined via high-pressure liquid chromatography and fluorescence detection. Data was analyzed via a population pharmacokinetic approach and nonlinear mixed effects modeling (NLME). Numerous covariates were examined in the NLME model.
Results: The absorption and elimination half-lives (t 1/2 ) were approximately 1.4 and 1 hour for pimobendan and 1.4 and 1.3 hours for ODMP, respectively. Pharmacokinetic parameters were highly variable, especially the values for pimobendan absorption and elimination rate, and absorption rate of ODMP with coefficients of variation of 147.84%, 64.51% and 64.49%, respectively. No covariate evaluated was a significant source of variability.
Conclusions and Clinical Importance: The pharmacokinetic parameters were highly variable among this group of dogs with MMVD. The variability was not associated with the dog's age, body weight or condition score, stage of heart disease, dose, serum creatinine, or alkaline phosphatase.
(© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)
Databáze: MEDLINE
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