Pharmacokinetics of posaconazole in koalas (Phascolarctos cinereus) after intravenous and oral administration |
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| Authors: | S. Gharibi B. Kimble L. Vogelnest J. Barnes C. K. Stadler M. Govendir |
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| Affiliation: | 1. Sydney School of Veterinary Science, The University of Sydney, Camperdown, NSW, Australia;2. Taronga Zoo, Mosman, NSW, Australia;3. Santa Barbara Zoo, Santa Barbara, CA, USA;4. Los Angeles Zoo, Los Angeles, CA, USA |
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| Abstract: | 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: 0.55–0.93 μg/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. |
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