Comparison of fluconazole and SDZ89-485 for therapy of experimental murine coccidioidomycosis

It is concluded that SDZ89-485 is more effective than fluconazole as treatment for experimental systemic coccidioidomycosis in mice, even though flu Conazole achieves higher peak levels in blood.

Abstract

We infected mice with arthroconidia of Coccidioides immitis by intraperitoneal injection and 48 h later treated them with either oral fluconazole or SDZ89-485, a new triazole. Both drugs completely inhibited fungal growth when administered at a dose of 50 mg/kg of body weight twice a day, but only SDZ89-485 was fully inhibitory at a dose of 5 mg/kg twice a day. In a second experiment, treatment with SDZ89-485 was delayed until 8 days after infection to allow infection to be well established before treatment. Both 5 and 50 mg/kg twice a day were effective regimens, which establishes that SDZ89-485 has activity against spherules in vivo. Mice that received fluconazole (50 mg/kg twice a day) had a peak level in blood of 60 micrograms/ml 1 h after a dose, but no measurable amount was found after 12 h. SDZ89-485 was more slowly absorbed, reaching a peak level in blood of 14 micrograms/ml at 12 to 15 h after a dose of 50 mg/kg. We conclude that SDZ89-485 is more effective than fluconazole as treatment for experimental systemic coccidioidomycosis in mice, even though fluconazole achieves higher peak levels in blood.