Fluconazole is a synthetic triazole antifungal agent widely used for the treatment and prevention of superficial and systemic fungal infections, particularly those caused by Candida species and Cryptococcus neoformans. It acts by inhibiting fungal cytochrome P450–dependent enzyme 14-α-demethylase, thereby disrupting ergosterol synthesis and compromising fungal cell membrane integrity. Historically, fluconazole was developed in the late 1970s and early 1980s by Pfizer as part of efforts to create safer, more selective azole antifungals with improved oral bioavailability and central nervous system penetration compared to earlier agents like ketoconazole. It was first approved for clinical use in 1990 and quickly gained prominence due to its favorable pharmacokinetics, high water solubility, ability to be administered both orally and intravenously, and relatively low toxicity. Over time, fluconazole became a cornerstone in antifungal therapy, especially in immunocompromised patients such as those with HIV/AIDS, transplant recipients, and cancer patients, while ongoing clinical use has also highlighted emerging resistance patterns that continue to shape antifungal research and stewardship.
