Clemons K V, Hanson L H, Stevens D A
Department of Medicine, Santa Clara Valley Medical Center, California.
Antimicrob Agents Chemother. 1993 May;37(5):1177-9. doi: 10.1128/AAC.37.5.1177.
The novel triazole D0870 was tested for in vitro activity, as well as in vivo in a murine model of pulmonary blastomycosis. In vitro, D0870 had inhibitory and fungicidal activity against Blastomyces dermatitidis (MIC = 0.048 microgram/ml; minimal fungicidal concentration = 0.097 microgram/ml). In vivo, D0870 was approximately 100-fold more active than fluconazole on the basis of milligrams per kilogram of body weight given once daily (QD) against blastomycosis. D0870 doses of both 1 or 10 mg/kg given QD and 10 or 100 mg/kg given every other day prolonged survival (P < 0.001) over fluconazole (100 mg/kg given QD). A D0870 dosage of 1 mg/kg QD was equivalent to fluconazole given at 100 mg/kg in reduction of lung burdens of B. dermatitidis, and D0870 administered at 10 mg/kg QD and 10 or 100 mg/kg every other day caused greater reduction (P < 0.001). However, D0870 at 100 mg/kg given QD was lethally toxic, whereas fluconazole at 100 mg/kg was not. These results indicate that D0870 is an effective therapy for murine blastomycosis and should be further tested.
新型三唑类药物D0870进行了体外活性测试，并在肺部芽生菌病的小鼠模型中进行了体内测试。在体外，D0870对皮炎芽生菌具有抑制和杀菌活性（MIC = 0.048微克/毫升；最低杀菌浓度 = 0.097微克/毫升）。在体内，基于每日一次（QD）给予的每千克体重毫克数，D0870对芽生菌病的活性比氟康唑高约100倍。每日一次给予1或10毫克/千克剂量的D0870以及隔日给予10或100毫克/千克剂量的D0870均能延长生存期（P < 0.001），优于氟康唑（每日一次给予100毫克/千克）。每日一次给予1毫克/千克剂量的D0870在降低皮炎芽生菌肺部负荷方面与给予100毫克/千克氟康唑相当，而每日一次给予10毫克/千克剂量的D0870以及隔日给予10或100毫克/千克剂量的D0870能使肺部负荷降低更多（P < 0.001）。然而，每日一次给予100毫克/千克剂量的D0870具有致命毒性，而给予100毫克/千克剂量的氟康唑则没有。这些结果表明D0870是治疗小鼠芽生菌病的有效疗法，应进一步进行测试。
