Voriconazole is a triazole antifungal agent used to treat invasive fungal infections, generally seen in patients who are immunocompromised. It has an increased affinity to 14-alpha sterol demethylase, and therefore makes it useful against fluconazole-resistant fungal infections. It is taken orally and used to treat esophageal candidiasis, cadidemia, invasive pulmonary aspergillosis, and serious fungal infections caused by Scedosporium apiospermum and Fusarium spp. Voriconazole is effective against all Candida species (including those resistant to other antifungal drugs), Cryptococcus neoformans, Trichosporon beigelii, and Saccharomyces cerevisiae. Voriconazole inhibits and antagonizes the production of ergosterol by inhibiting Lanosterol 14-alpha demethylase. It has a higher affinity for Lanosterol 14-alpha demethylase than other antifungal agents. Lanosterol 14-alpha demethylase is the enzyme that catalyzes the synthesis of 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol from lanosterol. With this enzyme inhibited ergosterol synthesis cannot occur which causes a significant low concentration of ergosterol in the fungal cell. Ergosterol is essential in maintaining membrane integrity in fungi. Without ergosterol, the fungus cell cannot synthesize membranes thereby increasing fluidity and preventing growth of new cells. With fungal growth limited, it allows the immune system to destroy the fungal cells.

Voriconazole Pathway References