Pharmacokinetics of fluconazole after oral administration to healthy beagle dogs

Abstract

Background: 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. Objectives: This study aimed to determine the plasma concentration of fluconazole after single and multiple administrations at two different dosages in dogs. Methods and materials: Eight healthy beagle dogs were divided into two groups, and each group received either 5 or 10 mg/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. Results: In the 5 mg/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 10 mg/kg group, the Cmax and AUC0-24h were 5.67？μg/mL and 109.19？μg*h/mL, respectively, after single administration and 15.10 μg/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 5 mg/kg group than those in the 10 mg/kg group at multiple administrations. Conclusions and clinical relevance: 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.