Clemons K V, Homola M E, Stevens D A
California Institute for Medical Research, Santa Clara Valley Medical Center, San Jose 95128, USA.
Antimicrob Agents Chemother. 1995 May;39(5):1169-72. doi: 10.1128/AAC.39.5.1169.
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.
新型三唑类化合物SCH 51048针对粗球孢子菌的活性进行了测试。SCH 51048在体外可抑制粗球孢子菌；13株分离菌的最低抑菌浓度（MIC）范围为≤0.39至0.78微克/毫升，最低杀菌浓度范围为≤0.39至1.6微克/毫升。在体内，以2至50毫克/千克体重给予SCH 51048或每千克给予100毫克氟康唑或伊曲康唑治疗的小鼠，均未死于系统性球孢子菌病，而对照组小鼠的死亡率为60%至100%。以25或50毫克/千克给予SCH 51048具有治愈效果，而每千克给予100毫克氟康唑或伊曲康唑则无治愈效果。药代动力学研究表明，血清中的峰值水平>14微克/毫升，估计半衰期>12小时。SCH 51048比氟康唑或伊曲康唑优越5至50倍或更多。
