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两性霉素B胶体分散体(安浮西)概述。

Overview of amphotericin B colloidal dispersion (amphocil).

作者信息

Stevens D A

机构信息

Department of Medicine, Santa Clara Valley Medical Center, San Jose, California 95128-2699.

出版信息

J Infect. 1994 May;28 Suppl 1:45-9. doi: 10.1016/s0163-4453(94)95971-4.

Abstract

Amphotericin B colloidal dispersion (ABCD) is an equimolar mixture of amphotericin B and cholesteryl sulphate with desirable preparation and stability characteristics. It allows the intravenous delivery of amphotericin B in doses up to 7 mg/kg daily. Peak serum concentrations of amphotericin B, given as ABCD, are lower, AUC0-infinity similar and half-life longer than deoxycholate amphotericin B. In vitro activity may be altered with respect to the deoxycholate preparation, some isolates being more resistant and others more susceptible. Preclinical toxicology with ABCD revealed a safety factor of five to 19-fold compared with deoxycholate amphotericin B. Animal models of coccidioidomycosis, disseminated cryptococcosis, candidiasis and invasive aspergillosis indicated a better therapeutic ratio, especially in cryptococcosis. Phase I/II studies in humans demonstrate efficacy against coccidioidomycosis, candidiasis and aspergillosis at doses from 1-7 mg/kg/day in at least 100 patients. Renal toxicity was acceptable but infusion-related side effects and anaemia were common. Side effects appear to decrease on therapy. Comparative studies with deoxycholate amphotericin B are needed.

摘要

两性霉素B胶体分散体(ABCD)是两性霉素B与硫酸胆固醇的等摩尔混合物,具有理想的制剂和稳定性特征。它允许每日静脉注射高达7mg/kg剂量的两性霉素B。以ABCD形式给药时,两性霉素B的血清峰值浓度较低,AUC0-∞相似,半衰期比去氧胆酸盐两性霉素B更长。与去氧胆酸盐制剂相比,其体外活性可能会有所改变,一些分离株更具抗性,而另一些则更敏感。ABCD的临床前毒理学显示,与去氧胆酸盐两性霉素B相比,安全系数为5至19倍。球孢子菌病、播散性隐球菌病、念珠菌病和侵袭性曲霉病的动物模型表明其治疗指数更佳,尤其是在隐球菌病中。在至少100名患者中进行的I/II期人体研究表明,在1-7mg/kg/天的剂量下对球孢子菌病、念珠菌病和曲霉病有效。肾毒性可接受,但与输注相关的副作用和贫血很常见。副作用似乎在治疗过程中会减少。需要与去氧胆酸盐两性霉素B进行对比研究。

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