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.

Keywords: Crossover study; O-desmethyl pimobendan; UDCG-212; Variability; Vetmedin.