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

Abstract

BackgroundPimobendan is an important therapy for dogs with myxomatous mitral valve disease (MMVD). The pharmacokinetics are reported in healthy dogs but not in dogs with heart disease.Hypothesis/ObjectivesTo determine if dog characteristics such as age, breed, body condition score, ACVIM stage of heart disease or biochemical laboratory value alter the pharmacokinetics of orally administered pimobendan and its metabolite in a cohort of dogs with naturally occurring MMVD.AnimalsFifty‐seven client‐owned dogs with MMVD ACVIM Stage B2, C, or D and administered pimobendan to steady state blood concentrations.MethodsProspective, observational study. Samples were collected using a sparse‐sampling protocol at specific intervals after administration of pimobendan. Plasma pimobendan and the active metabolite (O‐desmethyl‐pimobendan, ODMP) concentrations were determined via high‐pressure liquid chromatography and fluorescence detection. Data was analyzed via a population pharmacokinetic approach and nonlinear mixed effects modeling (NLME). Numerous covariates were examined in the NLME model.ResultsThe absorption and elimination half‐lives (t1/2) were approximately 1.4 and 1 hour for pimobendan and 1.4 and 1.3 hours for ODMP, respectively. Pharmacokinetic parameters were highly variable, especially the values for pimobendan absorption and elimination rate, and absorption rate of ODMP with coefficients of variation of 147.84%, 64.51% and 64.49%, respectively. No covariate evaluated was a significant source of variability.Conclusions and Clinical ImportanceThe pharmacokinetic parameters were highly variable among this group of dogs with MMVD. The variability was not associated with the dog's age, body weight or condition score, stage of heart disease, dose, serum creatinine, or alkaline phosphatase.

Changes in echocardiographic indices and left ventricular strain values by two-dimensional speckle-tracking echocardiography following pre-anesthetic oral pimobendan administration compared with intravenous pimobendan in dogs

“…Of these parameters, ESVI, LVIDSN, FS, EF, and E wave remained statistically unchanged from the Compared to the values of the Control group at the same timepoint, the PIMO PO group showed significant differences in FS and EF at T30, and in CI, ESVI, LVIDSN, FS, EF, LA/Ao, IVCT, and LVET at T60. This suggests that the effect of oral pimobendan was enhanced up to 90 min after administration, which is consistent with previous studies on the pharmacokinetics of oral pimobendan (34,35). In one study, maximal cardiovascular effects were observed 2-4 h after a single oral dose (0.26-0.28 mg/kg) in healthy dogs (35) whereas, in another study, the mean time to peak concentration with a single oral dose of pimobendan in dogs with MMVD was 1.66 h, independent of the ACVIM stage (34).…”

“…This suggests that the effect of oral pimobendan was enhanced up to 90 min after administration, which is consistent with previous studies on the pharmacokinetics of oral pimobendan (34,35). In one study, maximal cardiovascular effects were observed 2-4 h after a single oral dose (0.26-0.28 mg/kg) in healthy dogs (35) whereas, in another study, the mean time to peak concentration with a single oral dose of pimobendan in dogs with MMVD was 1.66 h, independent of the ACVIM stage (34).…”