Open AccessComparison of fluconazole and SDZ89-485 for therapy of experimental murine coccidioidomycosis
Author(s) -
Joshua Fierer,
Theo N. Kirkland,
Fred Finley
Publication year - 1990
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.34.1.13
Subject(s) - fluconazole , coccidioides , in vivo , coccidioides immitis , mycosis , pharmacology , medicine , body weight , oral administration , immunology , antifungal , biology , microbiology and biotechnology
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.