Clark J M, Whitney R R, Olsen S J, George R J, Swerdel M R, Kunselman L, Bonner D P
Department of Microbiology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Antimicrob Agents Chemother. 1991 Apr;35(4):615-21. doi: 10.1128/AAC.35.4.615.
The amphotericin B lipid complex (ABLC), which is composed of amphotericin B and the phospholipids dimyristoyl phosphatidylcholine and dimyristoyl phosphatidylglycerol, was evaluated for its acute toxicity in mice and for its efficacy in mice infected with a variety of fungal pathogens. ABLC was markedly less toxic to mice when it was administered intravenously; it had a 50% lethal dose of greater than 40 mg/kg compared with a 50% lethal dose of 3 mg/kg for Fungizone, the desoxycholate form of amphotericin B. ABLC was efficacious against systemic infections in mice caused by Candida albicans, Candida species other than C. albicans, Cryptococcus neoformans, and Histoplasma capsulatum. ABLC was also efficacious in immunocompromised animals infected with C. albicans, Aspergillus fumigatus, and H. capsulatum. Against some infections, the efficacy of ABLC was comparable to that of Fungizone, while against other infections Fungizone was two- to fourfold more effective than ABLC. Against several infections. Fungizone could not be given at therapeutic levels because of intravenous toxicity. ABLC, with its reduced toxicity, could be administered at drug levels capable of giving a therapeutic response. ABLC should be of value in the treatment of severe fungal infections in humans.
两性霉素B脂质复合物(ABLC)由两性霉素B与磷脂二肉豆蔻酰磷脂酰胆碱和二肉豆蔻酰磷脂酰甘油组成,对小鼠进行了急性毒性评估,并对感染多种真菌病原体的小鼠进行了疗效评估。静脉给药时,ABLC对小鼠的毒性明显较低;其半数致死剂量大于40mg/kg,而两性霉素B的去氧胆酸盐形式Fungizone的半数致死剂量为3mg/kg。ABLC对由白色念珠菌、非白色念珠菌属念珠菌、新型隐球菌和荚膜组织胞浆菌引起的小鼠全身感染有效。ABLC对感染白色念珠菌、烟曲霉和荚膜组织胞浆菌的免疫受损动物也有效。在某些感染中,ABLC的疗效与Fungizone相当,而在其他感染中,Fungizone的效果比ABLC高两到四倍。对于几种感染,由于静脉毒性,无法给予治疗剂量的Fungizone。ABLC毒性较低,可以给予能产生治疗反应的药物水平。ABLC在治疗人类严重真菌感染方面应具有价值。