Pharmacokinetics of fluconazole after oral administration to healthy beagle dogs

Abstract

Fluconazole can be effective in the treatment of superficial mycoses in dogs. However, the pharmacokinetics of fluconazole have not yet been evaluated to determine its optimal dosing regimen. This study aimed to determine the plasma concentration of fluconazole after single and multiple administrations at two different dosages in dogs. Eight healthy beagle dogs were divided into two groups, and each group received either 5 or 10mg/kg of fluconazole per os. The pharmacokinetics of fluconazole was determined following single and multiple administrations p.o. Single- and multiple-dose treatment periods were separated by a washout period of seven days. Plasma concentrations of fluconazole were determined by established high-performance liquid chromatography coupled with tandem mass spectrometry system. In the 5mg/kg group, the mean maximum concentrations (Cmax ) and the area under the plasma concentrations (AUC0-24h ) were 4.84 μg/mL and 85.56 μg*h/mL, respectively, after single administration and 6.58 μg/mL and 119.52 μg*h/mL, respectively, after multiple administrations. In the 10mg/kg group, the Cmax and AUC0-24h were 5.67 μg/mL and 109.19 μg*h/mL, respectively, after single administration and 15.10μg/mL and 291.51 μg*h/mL, respectively, after multiple administrations. The Cmax (p< 0.001) and AUC0-24h (p< 0.001) were significantly lower in the 5mg/kg group than those in the 10mg/kg group at multiple administrations. Fluconazole accumulates in plasma and exhibits dose-proportional pharmacokinetics after multiple doses, and was safe and well tolerated at these doses for short-term administration.