Safety and pharmacokinetics of single oral and intravenous doses of fluconazole in healthy subjects

Abstract

At intervals of two to four weeks, eight subjects received 25 mg of fluconazole orally; 50 mg orally; 25 mg intravenously; 50 mg intravenously; and then 100 mg orally (six subjects). Physical examinations and laboratory tests performed before and after each drug administration revealed no side effects or significant changes in test results. After oral administration, plasma fluconazole levels rose rapidly in a dose-dependent manner, maximum levels being reached in 0.7 hours after 25 mg, in 1.4 hours after 50 mg, and in 1.7 hours after 100 mg. After intravenous administration, mean plasma drug levels were higher than after oral administration for 30 minutes and then declined rapidly; at one hour after injection, plasma levels were similar to those seen after oral administration. During 120 hours after oral administration, 69% of the 25-mg dose, 66% of the 50-mg dose, and 75% of the 100-mg dose were recovered unchanged in urine; after intravenous injection, 74% of the 25-mg dose and 72% of the 50-mg dose were recovered. The half-life of fluconazole was 31 to 37 hours after oral and intravenous administration. Calculations of the areas under the plasma fluconazole time curves showed a clear dose-dependent response. The results indicate that fluconazole is a safe and effective antifungal agent.