Torrado J J, Espada R, Ballesteros M P, Torrado-Santiago S
Dpto Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Complutense University of Madrid, Plaza Ramón y Cajal, 28040 Madrid, Spain.
J Pharm Sci. 2008 Jul;97(7):2405-25. doi: 10.1002/jps.21179.
Amphotericin B is a low-soluble polyene antibiotic which is able to self-aggregate. The aggregation state can modify its activity and pharmacokinetical characteristics. In spite of its high toxicity it is still widely employed for the treatment of systemic fungal infections and parasitic disease and different formulations are marketed. Some of these formulations, such as liposomal formulations, can be considered as classical examples of drug targeting. The pharmacokinetics, toxicity and activity are clearly dependent on the type of amphotericin B formulation. New drug delivery systems such as liposomes, nanospheres and microspheres can result in higher concentrations of AMB in the liver and spleen, but lower concentrations in kidney and lungs, so decreasing its toxicity. Moreover, the administration of these drug delivery systems can enhance the drug accessibility to organs and tissues (e.g., bone marrow) otherwise inaccessible to the free drug. During the last few years, new AMB formulations (AmBisome, Abelcet, and Amphotec) with an improved efficacy/toxicity ratio have been marketed. This review compares the different formulations of amphotericin B in terms of pharmacokinetics, toxicity and activity and discusses the possible drug targeting effect of some of these new formulations.
两性霉素B是一种低溶解性的多烯抗生素，能够自我聚集。聚集状态可改变其活性和药代动力学特性。尽管其毒性较高，但仍被广泛用于治疗全身性真菌感染和寄生虫病，并且有不同的制剂上市销售。其中一些制剂，如脂质体制剂，可被视为药物靶向的经典例子。其药代动力学、毒性和活性明显取决于两性霉素B制剂的类型。脂质体、纳米球和微球等新型药物递送系统可使肝脏和脾脏中两性霉素B的浓度升高，但肾脏和肺部中的浓度降低，从而降低其毒性。此外，这些药物递送系统的给药可增强药物对自由药物难以到达的器官和组织（如骨髓）的可及性。在过去几年中，具有改善的疗效/毒性比的新型两性霉素B制剂（安必素、阿贝西普和两性霉素B脂质复合体）已上市销售。本综述比较了两性霉素B不同制剂在药代动力学、毒性和活性方面的差异，并讨论了其中一些新制剂可能的药物靶向作用。
