Vol.53 No.S-2 November 2005
Antifungal activity of voriconazole
Teikyo University Institute of Medical Mycology, 359 Otsuka, Hachioji, Tokyo, Japan
Abstract
Voriconazole (VRCZ), a new-generation azole antifungal agent with a wide antifungal spectrum, like all azole agents, selectively inhibits fungal ergosterol biosynthesis. We review experimental data obtained by Pfizer's research group and ours on the in vitro and in vivo antifungal activity of VRCZ compared to itraconazole (ITCZ) and fluconazole (FLCZ), along with data published elsewhere. VRCZ has substantial in vitro activity against Candida spp., including FLCZ-insusceptible C. glabrata and C. krusei, Cryptococcus neoformans and other yeasts that is similar to ITCZ and superior to FLCZ. VRCZ had potent and fungicidal in vitro activity against most Aspergillus spp. and several other mycelial fungi. In vivo VRCZ activity was evaluated in guinea pig models of systemic and invasive pulmonary aspergillosis and of systemic candidiasis due to a FLCZ-resistant C. albicans and C. krusei, using ITCZ and FLCZ as reference drugs. In all of these animal models, VRCZ was more effective than similar or higher doses of reference drugs in the survival of infected animals, clearance of challenged pathogenic fungi, and/or reduction of fungal burden in infected tissues. VRCZ thus appears to be an attractive option in the treatment of invasive and disseminated fungal infections.
Key word
voriconazole, new-generation azole antifungal agent, in vitro antifungal activity, selective action mechanism, in vivo antifungal activity
Received
July 8, 2005
Accepted
August 22, 2005
Jpn. J. Chemother. 53 (S-2): 8-15, 2005
