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.; 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 ) were 0.15 (0.13-0.18) L hr kg and 1.23 (0.93-1.53) L/kg, respectively. The median (range) elimination half-life (t ) 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 ; 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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“…Insertion of a blood collection catheter for Taronga Zoo koalas has been described previously (Gharibi et al, ). Blood (5 ml) was collected in lithium heparin tubes to establish baseline haematology and biochemistry ( t = 0 hr).…”

Posaconazole aggravates vincristine-related hypertension in children with acute lymphoblastic leukemia: a case report

“…If such a combination is still needed, calcium channel blocker-related side effects should be closely monitored, and the dosage of calcium channel blockers should be reduced if necessary. 13,14 Our study had limitations. Hypertension is a common side effect of dexamethasone, and both patients received dexamethasone concomitantly with vincristine and posaconazole.…”

Pharmacokinetic profile of oral and subcutaneous administration of paracetamol in the koala (Phascolarctos cinereus) and prediction of its analgesic efficacy

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