Population pharmacokinetics of single dose oral pimobendan in the ferret (Mustela putorius furo)

Background

Therapeutic options and dosing recommendations for congestive heart failure in the domestic ferret are currently extrapolated from domestic dogs and cats. The goal of this study was to determine the pharmacokinetics of oral pimobendan in the domestic ferret.

Methods

Twelve domestic ferrets were administered a single dose (average 0.4 mg/kg) of pimobendan in a commercially available, chewable, meat-flavored tablet formulation. High-performance liquid chromatography and fluorescence detection were used to measure pimobendan and the metabolite O-desmethylpimobendan (ODMP) in plasma samples collected at 0, 0.25, 0.5, 1, 2, 4, 6, 9, and 12 hours after administration using a sparse sampling protocol.

Results

Pharmacokinetic parameters for pimobendan and ODMP were as follows: peak plasma concentration, 14.29 ng/mL and 16.88 ng/mL; time to peak plasma concentration, 1.69 hours and 1.97 hours; area under the curve, 129.87 ng*h/mL and 190.97 ng*h/mL; and elimination half-life, 4.97 hours and 6.32 hours, respectively. No adverse events were noted.

Conclusions and clinical relevance

A single dose of oral pimobendan in ferrets reached concentrations higher than that reported for dogs by the manufacturer and similar to peak plasma concentrations correlated with a therapeutic effect in healthy dogs in a separate study. Individual variability was high and plasma concentrations in at least half of the ferrets remained at or below the lower limit of quantification throughout the duration of the study. Additional studies are needed to characterize the pharmacodynamics, oral bioavailability, and duration of action to facilitate dosing recommendations for pimobendan in the domestic ferret.