Fukasawa Masatomo
Sumitomo Pharmaceuticals Co., Ltd., Product Development Division, Tokyo, Japan.
Nihon Ishinkin Gakkai Zasshi. 2005;46(4):229-31. doi: 10.3314/jjmm.46.229.
Liposomal amphotericin B (AmBisome) is a DDS (drug delivery system) formulation of amphotericin B (AMPH-B), and has been developed in an attempt to reduce the toxicity of AMPH-B while retaining its therapeutic efficacy. AMPH-B has been the "gold standard" of antifungal therapy over the past four decades. It has a broad spectrum of fungicidal activity against a number of clinically important pathogens including Aspergillus and Candida. The mechanism of action of AMPH-B involves binding to ergosterol, the principal sterol in fungal cell membranes. Binding to ergosterol causes an increase in fungal membrane permeability, electrolyte leakage, and cell death. AMPH-B has affinity for cholesterol in mammalian membranes, which leads to severe side-effects including kidney damage. AmBisome is a unilamellar vesicle composed of AMPH-B and phospholipid. Upon administration, AmBisome remains intact in the blood and distributes to the tissues where fungal infection may occur, and is disrupted after attachment to the outside of fungal cells, resulting in fungal cell death. AmBisome and AMPH-B show similar in vitro and in vivo antifungal activity and clinical efficacy. However, AmBisome has less infusion-related toxicity and nephrotoxicity than AMPH-B.
脂质体两性霉素B（安必素）是两性霉素B（AMPH-B）的一种药物递送系统（DDS）制剂，其研发旨在降低AMPH-B的毒性，同时保留其治疗效果。在过去的四十年里，AMPH-B一直是抗真菌治疗的“金标准”。它对包括曲霉菌和念珠菌在内的多种临床上重要的病原体具有广谱杀菌活性。AMPH-B的作用机制包括与真菌细胞膜中的主要固醇麦角固醇结合。与麦角固醇结合会导致真菌膜通透性增加、电解质泄漏和细胞死亡。AMPH-B对哺乳动物细胞膜中的胆固醇具有亲和力，这会导致包括肾损伤在内的严重副作用。安必素是一种由AMPH-B和磷脂组成的单层囊泡。给药后，安必素在血液中保持完整，并分布到可能发生真菌感染的组织中，在附着于真菌细胞外部后被破坏，导致真菌细胞死亡。安必素和AMPH-B在体外和体内均显示出相似的抗真菌活性和临床疗效。然而，安必素的输液相关毒性和肾毒性比AMPH-B小。
