Fluconazole is a popular antifungal triazole drug whose efficacy has been proven in a large number of fungal infections, especially those transmitted by Candida species and Cryptococcus neoformans. Due to its good pharmacokinetic profiles, such as high oral bioavailability (>90%), predictable linear pharmacokinetics, and wide tissue distribution, fluconazole continues to be an important therapeutic agent in both systemic and central nervous system (CNS) infections. Its capability to produce high levels of cerebrospinal fluid also justifies its clinical application in diseases like cryptococcal meningitis. On a molecular scale, fluconazole selectively targets the fungal cytochrome P450 enzyme lanosterol 14-a-demethylase (ERG11), inhibiting ergosterol biosynthesis and destabilizing fungal cell membranes. It causes a rise in the membrane permeability, enzyme activity, and inhibition of fungal growth. Although its clinical application is common, and the overall safety profile is usually positive, the development of resistance has started to be a growing concern. The mechanisms of resistance are mutations of the ERG11 gene, overexpression of efflux transporters like CDR1 and MDR1, and changes in sterol biosynthesis pathways. Recent progres emphasizes the significance of antifungal stewardship, personalized dosing plans, and the creation of new drug delivery systems in order to improve the results of therapeutic interventions. This review will offer a critical and current knowledge of fluconazole, with a focus on its pharmacological characteristics, clinical significance, and the increasing problem of antifungal resistance.
Nikita Varfa (Mon,) studied this question.