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脂质体两性霉素B:稳定性、相容性及体外抗真菌活性

Amphotericin B in lipid emulsion: stability, compatibility, and in vitro antifungal activity.

作者信息

Walker S, Tailor S A, Lee M, Louie L, Louie M, Simor A E

机构信息

Department of Pharmacy, Sunnybrook Health Science Centre, University of Toronto, Ontario, Canada.

出版信息

Antimicrob Agents Chemother. 1998 Apr;42(4):762-6. doi: 10.1128/AAC.42.4.762.

Abstract

Newer formulations of amphotericin B (AmB) complexed with liposomes or lipid suspensions have been developed. Preliminary studies have suggested that AmB in Intralipid (IL) may be as effective as, but less toxic than, conventional formulations of AmB, but few data are available regarding its stability, compatibility, or in vitro antifungal activity. A compatibility study was done to evaluate the effects of AmB concentrations in IL containing either 10 or 20% soybean oil. The effects of temperature, shaking, and AmB and IL concentrations on the stability of AmB-IL suspensions were analyzed by visual inspection and liquid chromatography. The in vitro antifungal activity of AmB-IL, compared to that of AmB alone against reference strains of Candida species was determined by using a broth macrodilution method in accordance with National Committee for Clinical Laboratory Standards guidelines (M27-T). Samples of AmB-IL which were lightly shaken retained more than 90% of the AmB concentration over 21 days when stored at either 4 or 23 degrees C. Varying the AmB concentration did not appear to affect the stability of AmB-IL. However, a precipitate was formed when mixtures with more than 30% lipid as a proportion of the total volume were centrifuged. AmB-IL and AmB alone had similar in vitro antifungal activities against reference strains of yeasts. Further pharmacologic and clinical studies with AmB-IL are warranted, although AmB should not be combined with IL in concentrations capable of producing a precipitate.

摘要

已开发出与脂质体或脂质混悬液复合的新型两性霉素B(AmB)制剂。初步研究表明,脂质乳剂(IL)中的AmB可能与传统剂型的AmB效果相当,但毒性较小,但关于其稳定性、相容性或体外抗真菌活性的数据较少。进行了一项相容性研究,以评估含10%或20%大豆油的IL中AmB浓度的影响。通过目视检查和液相色谱分析温度、振荡以及AmB和IL浓度对AmB-IL混悬液稳定性的影响。根据美国国家临床实验室标准委员会指南(M27-T),采用肉汤稀释法测定AmB-IL与单独的AmB相比对念珠菌属参考菌株的体外抗真菌活性。轻度振荡的AmB-IL样品在4℃或23℃储存21天时,AmB浓度保持在90%以上。改变AmB浓度似乎不影响AmB-IL的稳定性。然而,当脂质占总体积比例超过30%的混合物离心时会形成沉淀。AmB-IL和单独的AmB对酵母参考菌株具有相似的体外抗真菌活性。尽管AmB不应与能产生沉淀浓度的IL混合,但仍有必要对AmB-IL进行进一步的药理学和临床研究。

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