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The clinical pharmacology of fluconazole.

The pharmacokinetic profile of fluconazole clearly distinguishes it from other antifungal agents; oral bioavailability is more than 90%, and plasma protein binding is 12%. The volume of distribution approximates that of total body water. Both peak and minimum plasma concentrations are linearly proportional to dose over a range of 50 to 400 mg. Fluconazole is metabolically stable. Renal clearance is the predominant route of elimination, with only 11% of a single dose excreted as metabolites. The mean elimination half-life is approximately 30 hours. Consequently, dosage requirements in the presence of renal insufficiency are predictable from and dependent on renal function. Fluconazole has been extensively studied regarding drug interactions that may occur during concomitant therapy with cimetidine, rifampin, warfarin, oral hypoglycemics, phenytoin, and cyclosporin A. Results indicate that fluconazole can be safely administered with these drugs, as well as a number of other commonly used drugs.