Pharmacokinetics of posaconazole in koalas (Phascolarctos cinereus) after intravenous and oral administration.

Abstract

The pharmacokinetic profile of posaconazole in clinically normal koalas (n=8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3mg/kg; n=2) or orally (p.o.; 6mg/kg; n=6) with serial plasma samples collected over 24 and 36hr, respectively. Plasma concentrations of posaconazole were quantified by validated high-performance liquid chromatography. A noncompartmental pharmacokinetic analysis of data was performed. Following i.v. administration, estimates of the median (range) of plasma clearance (CL) and steady-state volume of distribution (Vss ) were 0.15 (0.13-0.18) Lhr-1 kg-1 and 1.23 (0.93-1.53) L/kg, respectively. The median (range) elimination half-life (t1/2 ) after i.v. and p.o. administration was 7.90 (7.62-8.18) and 12.79 (11.22-16.24) hr, respectively. Oral bioavailability varied from 0.43 to 0.99 (median: 0.66). Following oral administration, maximum plasma concentration (Cmax ; median: 0.72, range: 0.55-0.93μg/ml) was achieved in 8 (range 6-12) hr. The in vitro plasma protein binding of posaconazole incubated at 37°C was 99.25±0.29%. Consideration of posaconazole pharmacokinetic/pharmacodynamic (PK/PD) targets for some yeasts such as disseminated candidiasis suggests that posaconazole could be an efficacious treatment for cryptococcosis in koalas.