Pappagianis D, Zimmer B L, Theodoropoulos G, Plempel M, Hector R F
Department of Medical Microbiology, School of Medicine, University of California, Davis 95616.
Antimicrob Agents Chemother. 1990 Jun;34(6):1132-8. doi: 10.1128/AAC.34.6.1132.
A new triazole, Bay R 3783, was compared with ketoconazole, itraconazole, and fluconazole, which were given via the alimentary tract at three dosages, and amphotericin B, which was given at 1 mg/kg intraperitoneally, in murine models of the systemic mycoses coccidioidomycosis, histoplasmosis, and blastomycosis. In a pulmonary coccidioidomycosis model, Bay R 3783, fluconazole, and itraconazole were essentially equally efficacious and more active than ketoconazole in protecting mice against death; but they were inferior to amphotericin B. In a short-term organ load experiment, Bay R 3783 and amphotericin B were equally effective and were more effective than the other drugs in reducing the amount of Coccidioides immitis in the lungs. Against meningocerebral coccidioidomycosis, Bay R 3783, itraconazole, and fluconazole at 25 mg/kg and amphotericin B prevented death only during therapy, with mortalities ensuing shortly thereafter. In mice with systemic histoplasmosis, Bay R 3783 and itraconazole at 25 mg/kg and amphotericin B prevented death in all mice through a 44-day observation period. Clearance of Histoplasma capsulatum from organs was similar in mice treated with Bay R 3783 and itraconazole; this clearance was greater than that in mice treated with ketoconazole and fluconazole but less than that in mice treated with amphotericin B. In mice with systemic blastomycosis, Bay R 3783 at 25 mg/kg yielded 90% survivors at 60 days, which was greater than that achieved with amphotericin B (60%) or itraconazole (30%). Clearance of Blastomyces dermatitidis from the lungs was greatest with Bay R 3783, followed by that with amphotericin B, itraconazole, fluconazole, and ketoconazole, in that order. Therefore, Bay R 3783 showed effectiveness comparable to or exceeding those of itraconazole and fluconazole and exceeding that of ketoconazole against these systemic mycoses in mice.
在系统性球孢子菌病、组织胞浆菌病和芽生菌病的小鼠模型中，将一种新型三唑类药物Bay R 3783与酮康唑、伊曲康唑和氟康唑进行了比较，这三种药物经消化道给予三种剂量，同时还将其与腹腔注射1mg/kg的两性霉素B进行了比较。在肺部球孢子菌病模型中，Bay R 3783、氟康唑和伊曲康唑在保护小鼠免于死亡方面基本同样有效，且比酮康唑更具活性；但它们不如两性霉素B。在一项短期器官负荷实验中，Bay R 3783和两性霉素B同样有效，且在减少肺部粗球孢子菌数量方面比其他药物更有效。针对脑膜脑球孢子菌病，Bay R 3783、伊曲康唑和25mg/kg的氟康唑以及两性霉素B仅在治疗期间预防了死亡，此后不久便出现了死亡。在患有系统性组织胞浆菌病的小鼠中，Bay R 3783、25mg/kg的伊曲康唑和两性霉素B在44天的观察期内防止了所有小鼠死亡。用Bay R 3783和伊曲康唑治疗的小鼠中，荚膜组织胞浆菌从器官中的清除情况相似；这种清除率高于用酮康唑和氟康唑治疗的小鼠，但低于用两性霉素B治疗的小鼠。在患有系统性芽生菌病的小鼠中，25mg/kg的Bay R 3783在60天时产生了90%的存活率，高于两性霉素B（60%）或伊曲康唑（30%）。Bay R 3783使肺部皮炎芽生菌的清除率最高，其次是两性霉素B、伊曲康唑、氟康唑和酮康唑，顺序依次如此。因此，在小鼠中，Bay R 3783对这些系统性真菌病的有效性与伊曲康唑和氟康唑相当或超过它们，且超过酮康唑。
