Activities of the triazole SCH 51048 against Coccidioides immitis in vitro and in vivo.
The activity of the novel triazole SCH 51048 was tested against Coccidioides immitis. SCH 51048 inhibited C. immitis in vitro; MICs for 13 isolates ranged from < or = 0.39 to 0.78 micrograms/ml, and minimum fungicidal concentrations ranged from < or = 0.39 to 1.6 micrograms/ml. In vivo, no mice treated with SCH 51048 at 2 to 50 mg/kg of body weight or 100 mg of fluconazole or itraconazole per kg died of systemic coccidioidomycosis, whereas 60 to 100% of the control mice died. SCH 51048 given at 25 or 50 mg/kg was curative, whereas fluconazole or itraconazole given at 100 mg/kg was not curative. Pharmacokinetic studies showed peak levels in serum of > 14 micrograms/ml, with an estimated half-life of > 12 h. SCH 51048 was 5- to 50-fold or more superior to fluconazole or itraconazole.
Clemons
K V
KV
California Institute for Medical Research, Santa Clara Valley Medical Center, San Jose 95128, USA.
Homola
M E
ME
Stevens
D A
DA
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D003045:Coccidioides / Q000187:drug effects*; D003047:Coccidioidomycosis / Q000188:drug therapy* / Q000382:microbiology*; D005260:Female; D015725:Fluconazole / Q000493:pharmacokinetics / Q000627:therapeutic use; D006207:Half-Life; D017964:Itraconazole / Q000493:pharmacokinetics / Q000627:therapeutic use; D051379:Mice; D008826:Microbial Sensitivity Tests; D014230:Triazoles / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*
D000935:Antifungal Agents; C094161:SCH 51048; D014230:Triazoles; D017964:Itraconazole; D015725:Fluconazole