Preclinical antimycotic activity of SDZ 89–485: a new orally and topically effective triazole

Abstract

SDZ 89-485 is a new orally and topically active triazole antifungal with efficacy superior to reference compounds in most animal infection models used for preclinical comparison of antifungals. The compound inhibits mycelial transformation of Candida albicans in vitro at MIC50 concentrations of 0.006 and 0.00019 mg l-1 in MEM and NYP medium, respectively. In rodent models of vaginal candidosis SDZ 89-485 was significantly more active than reference compounds after various oral or topical treatment regimens, with ED50 values ranging from 0.09 to 0.79 mg kg-1 and 0.01% active ingredient, respectively. When administered orally, the efficacy of SDZ 89-485 was superior to, or as good as that of the reference compounds in several murine models of systemic candidosis, sporotrichosis and histoplasmosis. In murine aspergillosis, using the kidney as the target organ. SDZ 89-485 was as active as itraconazole. Guinea pig trichophytosis was more responsive to oral fluconazole and itraconazole than to oral SDZ 89-485.