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

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.

• Authors: J Fierer, T Kirkland, F Finley
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 34 Issue 1 Pg. 13-6 (Jan 1990) ISSN: 0066-4804 [Print] United States
• PMID: 2327748 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antifungal Agents
• Triazoles
• SDZ 89-485
• Fluconazole

Topics

• Animals
• Antifungal Agents (pharmacokinetics, therapeutic use)
• Coccidioides
• Coccidioidomycosis (drug therapy, microbiology)
• Female
• Fluconazole (pharmacokinetics, therapeutic use)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred DBA
• Triazoles (pharmacokinetics, therapeutic use)