Pharmacokinetics and bioavailability of itraconazole oral solution in cats.
OBJECTIVE
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
The disposition of ITR oral solution in cats is characterised by a long terminal half-life, a short peak time and moderate bioavailability.
National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Chaoping
C
Liang
Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, China.
Qi
Q
Shan
National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Jialian
J
Zhong
National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Wei
W
Li
National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Xiufeng
X
Zhang
Guangzhou Senya Animal's Pharmaceutical Co Ltd, Guangzhou, China.
Jing
J
Wang
National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Changfu
C
Cao
National Reference Laboratory of Veterinary Drug Residues (SCAU), College of Veterinary Medicine, South China Agricultural University, Guangzhou, China zlzeng@scau.edu.cn.
Zhenling
Z
Zeng
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002371:Cat Diseases / Q000188:drug therapy; D002415:Cats / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D065692:Cytochrome P-450 CYP3A Inhibitors / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D017964:Itraconazole / Q000493:pharmacokinetics*; D019999:Pharmaceutical Solutions
D065692:Cytochrome P-450 CYP3A Inhibitors; D019999:Pharmaceutical Solutions; D017964:Itraconazole