Antifungal activity of the new azole UK-109, 496 (voriconazole)

The in vitro activity of voriconazole fully includes Aspergillus, and also emerging moulds like Fusarium, Pseudallescheria boydii, and Penicillium mar neffei. The minimal inhibitory concentrations of voriconazole for Candida k rusei and Candida glabrata, which are resistant or less susceptible to fluc onazole, promise clinical efficacy, although they are ten times higher (0.3 0-0.39 mu g/ml) than those for Candida albicans and other Candida spp. (0.0 01-0.05 mu g/ml). The endemic fungal pathogens Histoplasma capsulatum, Cocc idioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis, as well as Cryptococcus neoformans, and the dermatophytes are also fully su sceptible 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 administer ed in doses between 2.5 and 45 mg/kg/day. The pharmacokinetics of voriconaz ole in man produced sustained high blood and tissue levels following oral a nd intravenous applications of 50 to 200 mg/day. Side effects included full y reversible mild to moderate visual disturbances (8 to 44 %) and raised li ver function enzymes (6 to 8%). In conclusion, voriconazole is highly active against Aspergillus and most o ther medically relevant fungi, it is applicable intravenously, and it appea rs to have an acceptable safety profile.