Pharmacokinetics of fluconazole following intravenous and oral administration and body fluid concentrations of fluconazole following repeated oral dosing in horses

Objective-To determine the pharmacokinetics of fluconazole in horses. Animals-6 clinically normal adult horses. Procedure-Fluconazole (10 mg/kg of body weight) was administered intravenou sly or orally with 2 weeks between treatments. Plasma fluconazole concentra tions were determined prior to and 10, 20, 30, 40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after administration. A long-te rm oral dosing regimen was designed in which all horses received a loading dose of fluconazole (14 mg/kg) followed by 5 mg/kg every 24 hours for 10 da ys. Fluconazole concentrations were determined in aqueous humor, plasma, CS F synovial fluid, and urine after administration of the final dose. Results-Mean ( SD) apparent volume of distribution of fluconazole at steady state was 1.21 +/- 0.01 L/kg. Systemic availability and time to maximum pl asma concentration following oral administration were 101.24 +/- 27.50% and 1.97 +/- 1.68 hours, respectively. Maximum plasma concentrations and termi nal half-lives after IV and oral administration were similar. Plasma, CSF s ynovial fluid, aqueous humor, and urine concentrations of fluconazole after long-term oral administration of fluconazole were 30.50 +/- 23.88, 14.99 /- 1.86, 14.19 +/- 5.07, 11.39 +/- 2.83, and 56.99 +/- 32.87 mug/ml, respec tively. Conclusions and Clinical Relevance-Bioavailability of fluconazole was high after oral administration to horses. Long-term oral administration maintain ed plasma and body fluid concentrations of fluconazole above the mean inhib itory concentration (8.0 mg/ml) reported for fungal pathogens in horses. Fl uconazole may be an appropriate agent for treatment of fungal infections in horses.