In vitro and in vivo antifungal activities of ER-30346, a novel oral triazole with a broad antifungal spectrum

ER-30346 is a novel oral triazole with a broad spectrum of potent activity against a nide range of fungi, ER-30346, with MICs at which 90% of the strains tested are inhibited (MIC(90)s) ranging from 0.025 to 0.78 mu g/ml, was 4 to 32 times more active than itraconazole, fluconazole, and amphotericin B against Candida albicans, Candida parapsilosis, and Candida glabrata, Against Candida tropicalis, ER-30346, with an MIC(90) of 12.5 mu g/ml, was 2 to >8 times more active than itraconazole and fluconazole, but was 16 times less active than amphotericin B, ER-30346 (MIC(90), 0.78 mu g/ml) was four to eight times more active than fluconazole and amphotericin B and had activity comparable to that of itraconazole against Trichosporon beigelli, The MIC(90)s of ER-30346 were 0.10 mu g/ml for Cryptococcus neoformans and 0.39 mu g/ml for Aspergillus fumigatus. ER-30346 was 2 to 8 times more active than itraconazole and amphotericin B and 32 to >256 times more active than fluconazole. ER-30346 also showed good activity against dermatophytes, with MICs ranging from 0.05 to 0.39 mu g/ml, and its activity was comparable to or 2 to 16 times higher than those of itraconazole and amphotericin B and >32 times higher than that of fluconazole, In vivo activity was evaluated with systemic infections in mice, Against systemic candidiasis and cryptococcosis, ER-30346 was comparable in efficacy to fluconazole and was more effective than itraconazole. Of the drugs tested, ER-30346 was the most effective drug against systemic aspergillosis. We studied the levels of ER-30346 in mouse plasma. The maximum concentration of drug in plasma and the area under the concentration-time curve for ER-30346 showed good linearity over a range of doses from 2 to 40 mg/kg of body weight.