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&#xa0;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&#xa0;mg/kg group, the mean maximum concentrations (C) and the area under the plasma concentrations (AUC) were 4.84&#x2009;&#x3bc;g/mL and 85.56&#x2009;&#x3bc;g*h/mL, respectively, after single administration and 6.58&#x2009;&#x3bc;g/mL and 119.52&#x2009;&#x3bc;g*h/mL, respectively, after multiple administrations. In the 10&#xa0;mg/kg group, the Cand AUCwere 5.67&#x2009;&#x3bc;g/mL and 109.19&#x2009;&#x3bc;g*h/mL, respectively, after single administration and 15.10&#xa0;&#x3bc;g/mL and 291.51&#x2009;&#x3bc;g*h/mL, respectively, after multiple administrations. The C(p&#xa0;<&#x2009;0.001) and AUC(p&#xa0;<&#x2009;0.001) were significantly lower in the 5&#xa0;mg/kg group than those in the 10&#xa0;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.