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JOURNAL ARTICLE
REVIEW
Antifungal activity of the new azole UK-109, 496 (voriconazole).
Mycoses 1999
The in vitro activity of voriconazole fully includes Aspergillus, and also emerging moulds like Fusarium, Pseudallescheria boydii, and Penicillium marneffei. The minimal inhibitory concentrations of voriconazole for Candida krusei and Candida glabrata, which are resistant or less susceptible to fluconazole, promise clinical efficacy, although they are ten times higher (0.30-0.39 microgram/ml) than those for Candida albicans and other Candida spp. (0.001-0.05 microgram/ml). The endemic fungal pathogens Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis, as well as Cryptococcus neoformans, and the dermatophytes are also fully susceptible to voriconazole. The zygomycetes and Sporothrix schenckii remain a problem. Voriconazole has been shown to be effective against invasive aspergillosis (IA) and fluconazole-resistant candidosis in animal models, when administered in doses between 2.5 and 45 mg/kg/day. The pharmacokinetics of voriconazole in man produced sustained high blood and tissue levels following oral and intravenous applications of 50 to 200 mg/day. Side effects included fully reversible mild to moderate visual disturbances (8 to 44%) and raised liver function enzymes (6 to 8%). In conclusion, voriconazole is highly active against Aspergillus and most other medically relevant fungi, it is applicable intravenously, and it appears to have an acceptable safety profile.
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