C10 - Comparison of Single-dose Pharmacokinetics in Dogs Receiving Vetmedin(R) and Two Formulations of Generic Pimobendan

Abstract: Background: Vetmedin® is commonly prescribed for the treatment of cardiac disease in dogs. Compounded formulations of generic pimobendan are commercially available and may offer more accurate dosing at a more affordable cost.

Hypothesis/Objectives: The aim of this study was to evaluate the pharmacokinetic biosimilarity of pimobendan and its active metabolite, O-deoxymethyl pimobendan (ODMP) following a single oral dose of Vetmedin® (V), pimobendan capsule (C), and pimobendan suspension (S) in healthy dogs.

Animals: Six healthy, purpose-bred research beagle dogs.

Methods: This was a randomized cross-over study. Each dog received one formulation of pimobendan at a mean dose of 0.33mg/kg (range: 0.3-0.35) and blood was collected for pharmacokinetic analysis; this was repeated for the other two formulations following a 48-hour washout period after administration of each formulation.

Results: Noncompartmental modeling was used. The pimobendan geometric mean Cmax was 51.9ng/mL(V), 51.2ng/mL(S), and 36.1ng/mL(C) while the ODMP Cmax was 45.3ng/ml(V), 44.5ng/ml(S), and 33.2ng/ml(C). AUC were compared between formulations using a hierarchical mixed model. The ratio of AUC between V and S fell within the a priori acceptable range for bioequivalence (1.01; 0.88-1.16 CrI 90%), while the AUC ratio between V and C was 1.17 (0.93-1.44 CrI 90%).

Conclusions and clinical importance: Pimobendan exposure was similar between the generic suspension and Vetmedin®, but lower with the generic capsule. The results support that generic suspension and Vetmedin® are clinically exchangeable. Generic pimobendan capsule may be clinically satisfactory based on available varying dosing strategies or may require dose adjustment.