Comparison of fluconazole and SDZ89-485 for therapy of experimental murine coccidioidomycosis.
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.
Fierer
J
J
Department of Medicine, Veterans Administration Medical Center, San Diego, California 92161.
Kirkland
T
T
Finley
F
F
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003045:Coccidioides; D003047:Coccidioidomycosis / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D015725:Fluconazole / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D014230:Triazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000935:Antifungal Agents; D014230:Triazoles; C060176:SDZ 89-485; D015725:Fluconazole