Vanazole Mechanism of Action

Pharmacology: Pharmacodynamics: Voriconazole is a triazole antifungal that in sensitive fungi inhibits cytochrome P450-dependent enzymes resulting in the impairment of ergosterol synthesis in fungal cell membranes. Voriconazole has a broad spectrum of activity against all Candida species, including fluconazole-resistant strains, as well as Aspergillus spp., Scedosporium spp., and Fusarium spp.
Pharmacokinetics: Voriconazole has non-linear pharmacokinetics due to saturable metabolism. It is rapidly and almost completely absorbed from the gastrointestinal tract. The oral bioavailability of voriconazole is estimated to be 96%. Peak plasma concentrations occur about 1 to 2 hours after an oral dose. Plasma protein binding of voriconazole is about 58%. The volume of distribution at steady state for voriconazole is estimated to be 4.6 L/kg. Voriconazole diffuses into CSF. Voriconazole is metabolized by hepatic cytochrome P450 isoenzyme CYP2C19; the major metabolite is the inactive N-oxide. Metabolism via isoenzymes CYP2C9 and CYP3A4 has also been shown in vitro. Half-life elimination is variable and dose-dependent. About 80% of voriconazole is excreted in the urine as inactive metabolites and with less than 2% as unchanged drug.