Pharmacokinetics and Tissue Penetration of Fluconazole in Humans

The pharmacokinetics and tissue/fluid penetration of fluconazole have been studied in more than 400 healthy individuals and various subsets of patients. The pharmacokinetics of fluconazole are similar following intravenous and oral dosing. Oral bioavailability is greater than 90%, and concentrations peak approximately 2 hours after dosing. The apparent volume of distribution is 0.7 L/kg, and plasma protein binding is low (12%). The drug is metabolically stable, with renal excretion accounting for approximately 80% of the elimination as unchanged drug. Repeated once-daily dosing results in an increase in plasma levels of approximately 2.5-fold, with steady state achieved by day 7. Plasma levels are dose-proportional, and the elimination rate remains constant across the dosage range and over time. The plasma half-life of fluconazole is approximately 30 hours. The pharmacokinetics are similar in healthy young adults and in the elderly, but dose modification is required in patients with renal impairment. Fluconazole diffuses readily into the cerebrospinal fluid, sputum, and saliva and is concentrated in the urine and skin.