title: Activities of the triazole SCH 51048 against Coccidioides immitis in vitro and in vivo.
abstract: 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.
authors.affiliation: California Institute for Medical Research, Santa Clara Valley Medical Center, San Jose 95128, USA.
authors.forename: K V
authors.initials: KV
authors.lastname: Clemons
authors.forename: M E
authors.initials: ME
authors.lastname: Homola
authors.forename: D A
authors.initials: DA
authors.lastname: Stevens
mesh_terms: 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*
chemical_list: D000935:Antifungal Agents; C094161:SCH 51048; D014230:Triazoles; D017964:Itraconazole; D015725:Fluconazole