Evaluation of bioequivalence of pimobendan oral solution and pimobendan oral capsules in healthy Beagle dogs

Abstract

Introduction/Objectives

This study aimed to determine the pharmacokinetics and bioequivalence of pimobendan administered as the originator reference product Vetmedin® pimobendan 5-mg capsules and a newly developed liquid formulation Vetmedin® pimobendan 1.5-mg/mL oral solution.

Animals

Pharmacokinetic profiles were investigated in 12 male and 12 female adult Beagle dogs.

Materials and Methods

The study was a randomized, four-period, two-sequence, full-replicate crossover design with maximum concentration (C_max) and area under the plasma concentration-time curve to last sampling time (AUC_0→last) used as pivotal bioequivalence parameters. For each treatment period, all animals were treated with a single dose of 5 mg/animal pimobendan, resulting in a dose of 0.33 mg/kg to 0.56 mg/kg. For each administration period, one predose and 15 postdose blood samples were taken over a period of 12 h. Plasma samples were analyzed for concentrations of pimobendan and the active metabolite O-desmethyl pimobendan.

Results

Both formulations were well tolerated. Bioequivalence of the test product pimobendan 1.5-mg/mL oral solution with the reference product pimobendan 5-mg capsules was demonstrated for both the parent compound pimobendan and the metabolite O-desmethyl pimobendan since the 90% confidence intervals of the ratios of C_max and AUC_0→last were entirely contained within the range of 0.8–1.25.

Study Limitations

The study was performed according to international guidelines with healthy dogs specifically bred for experimental purposes. Comparable data for client-own dogs are not available.

Conclusion

The new Vetmedin® pimobendan 1.5-mg/mL oral solution is a bioequivalent pharmaceutical preparation that is expected to improve dosing accuracy and compliance, especially in toy breed and small dogs.