Pharmacokinetics and bioavailability of itraconazole oral solution in cats.

Abstract

OBJECTIVES: The aim of this study was to describe the pharmacokinetics and bioavailability of itraconazole (ITR) oral solution in healthy cats. METHODS: The pharmacokinetics of ITR were studied in eight healthy, fasted cats after a single intravenous (IV) and oral (PO) administration at a dose of 5 mg/kg, in a two-period crossover design study. Blood was obtained at predetermined intervals for the determination of ITR concentrations with high-performance liquid chromatography. Pharmacokinetic characterisation was performed by a non-compartmental method using WinNonlin 5.2.1. RESULTS: After IV administration, the major pharmacokinetic parameters were as follows (mean ± SD): terminal elimination half-life (T1/2λz ) 15.8 ± 1.88 h; area under the curve from time zero to infinity (AUC0-∞ ) 13.9 ± 3.17 h·μg/ml; total body clearance 0.37 ± 0.08 l/h/kg; apparent volume of distribution 8.51 ± 1.92 l/kg; mean residence time 20.6 ± 3.95 h. After PO administration, the principal pharmacokinetic parameters were as follows (mean ± SD): T1/2λz 15.6 ± 3.20 h; AUC0-∞ 7.94 ± 2.83 h·μg/ml; peak concentration 0.70 ± 0.14 μg/ml; time of peak 1.43 ± 0.53 h. The absolute bioavailability of ITR oral solution after oral administration was 52.1 ± 11.6%. CONCLUSIONS AND RELEVANCE: The disposition of ITR oral solution in cats is characterised by a long terminal half-life, a short peak time and moderate bioavailability.