Pharmacokinetics of Single Dose Oral Pimobendan in Hispaniolan Amazon Parrots (Amazona ventralis)

摘要

Pimobendan (Vetmedin, Boehringer-Ingelheim, Saint Joseph, CO, USA) is a phosphodiesterase (PDE)-inhibitor and calcium sensitizer with inotropics and vasolidator properties used in the treatment of congestive heart failure. The mechanism of action is via inhibition of PDE III and V and by increasing intracellular calcium sensitivity in the cardiac myocardium,2 Pharmacokinetic and pharmacodynamic studies have been published in humans, dogs, and cats, but avian studies are lacking. Pimobendan has been used in birds at the empirical dosage of 0.25 mg/kg. To determine the pharmacokinetic parameters, 3 pilot crossover studies with 2 birds, each receiving 1, 3 and 10 mg/kg PO, provided the basis for 2 trials with 6 birds, each receiving 10 mg/kg PO using 2different suspensions. Blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 18 hours after drug administration. Plasma concentrations were determined by HPLC/MS by use of electrospray ionization. Pharmacokinetic analysis was performed withcomputer software (WinNonlin 5.2, Pharsight Corporation, Mountain View, CA, USA). Due to the erratic and low concentrations of pimobendan found in the plasma samples, pharmacokinetic analyses were performed using mean plasma concentrations at each timepoint for each suspension. Plasma concentrations after commercial pimobendan tablet suspension at 10 nig/kg reached a Cmax of 8.26 ng/L at 3 hours with a terminal half-life of 2.1 hours, while the bulk chemical suspension (Ontario Chemicals, Inc, Guelph,Ontario, CA) reached a Cmax of 1.28 ng/ml at 12 hours and had a terminal half-life of 2.3 hours.