An Expert Monograph on Fluconazole (DB00196)

Authored by a Senior Clinical Pharmacologist

Executive Summary

Fluconazole (DrugBank ID: DB00196) is a first-generation synthetic triazole antifungal agent that represents a cornerstone in the management of both superficial and life-threatening systemic mycoses. Since its approval by the U.S. Food and Drug Administration (FDA) in 1990, it has remained a widely prescribed medication, valued for its efficacy, convenient dosing, and availability in both oral and intravenous formulations. Its mechanism of action involves the highly selective inhibition of fungal cytochrome P450-dependent enzyme lanosterol 14-α-demethylase, a critical step in the biosynthesis of ergosterol. The subsequent disruption of fungal cell membrane integrity results in a primarily fungistatic effect against a broad spectrum of yeasts and dimorphic fungi.

The clinical utility of fluconazole is profoundly influenced by its exceptional pharmacokinetic profile, characterized by near-complete oral bioavailability (>90%), low plasma protein binding (11-12%), and extensive distribution into body tissues and fluids, including remarkable penetration into the cerebrospinal fluid (CSF). This latter property revolutionized the treatment of cryptococcal meningitis, enabling a shift from toxic parenteral therapies to effective oral management. The drug's long elimination half-life of approximately 30 hours facilitates convenient once-daily dosing. Elimination is predominantly renal, with about 80% of the drug excreted unchanged in the urine, a characteristic that necessitates dose adjustments in patients with renal impairment.