Pharmacokinetics and bioavailability of itraconazole oral solution in cats.

Abstract

The aim of this study was to describe the pharmacokinetics and bioavailability of itraconazole (ITR) oral solution in healthy cats. 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. 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%. The disposition of ITR oral solution in cats is characterised by a long terminal half-life, a short peak time and moderate bioavailability.