Pharmacokinetics of posaconazole in koalas (Phascolarcto scinereus) after intravenous and oral administration
S. Gharibi1, B. Kimble1, L. Vogelnest2, J. Barnes3, C. K. Stadler4, M. Govendir1
1Sydney School of Veterinary Science, The University of Sydney, Camperdown, NSW, Australia
2Taronga Zoo, Mosman, NSW, Australia
3Santa Barbara Zoo, Santa Barbara, CA, USA
4Los Angeles Zoo, Los Angeles, CA, USA
The pharmacokinetic profile of posaconazole in clinically normal koalas (n = 8) was investigated. Single doses of posaconazole were administered intravenously (i.v.; 3 mg/kg; n = 2) or orally (p.o.; 6 mg/kg; n = 6) with serial plasma samples collected over 24 and 36 hr, 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) L hr-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.