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Pharmacokinetics of posaconazole in koalas ( Phascolarctos cinereus ) after intravenous and oral administration
Author(s) -
Gharibi S.,
Kimble B.,
Vogelnest L.,
Barnes J.,
Stadler C. K.,
Govendir M.
Publication year - 2017
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12407
Subject(s) - phascolarctos cinereus , posaconazole , pharmacokinetics , pharmacology , medicine , physiology , dermatology , voriconazole , antifungal , population , environmental health
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 ( V ss ) 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 ( t 1/2 ) 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 ( C max ; 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.