Yardley V, Croft S L
Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, United Kingdom.
Antimicrob Agents Chemother. 1997 Apr;41(4):752-6. doi: 10.1128/AAC.41.4.752.
The polyene antibiotic amphotericin B is currently a second-line treatment for visceral leishmaniasis (VL) and mucocutaneous leishmaniasis. Lipid-amphotericin B formulations with lower toxicity than the parent drug that were developed for the treatment of systemic mycoses have proved to be an effective treatment for VL, especially AmBisome, a small unilamellar negatively charged liposome. In vitro, free amphotericin B was three to six times more active than the liposomal formulation AmBisome against both Leishmania major promastigotes in culture and amastigotes in murine macrophages. In a BALB/c L. major model of cutaneous infection, liposomal amphotericin B administered once a day on six alternate days by the intravenous route produced a dose-response effect between 6.25 and 50 mg/kg. Liposomal amphotericin B administered subcutaneously close to a lesion had no significant activity. Free drug was ineffective at nontoxic doses. The results suggest that liposomal amphotericin B may be useful in the treatment of cutaneous leishmaniasis.
多烯抗生素两性霉素B目前是治疗内脏利什曼病(VL)和黏膜皮肤利什曼病的二线药物。为治疗系统性真菌病而研发的毒性低于母体药物的脂质体两性霉素B制剂已被证明是治疗VL的有效药物,尤其是两性霉素B脂质体(AmBisome),一种小单室带负电荷的脂质体。在体外,游离两性霉素B对培养中的硕大利什曼原鞭毛体和小鼠巨噬细胞中的无鞭毛体的活性比脂质体制剂两性霉素B高3至6倍。在BALB/c小鼠皮肤感染硕大利什曼原虫的模型中,通过静脉途径每隔一天给药一次,连续六天给予脂质体两性霉素B,在6.25至50mg/kg之间产生了剂量反应效应。在靠近病灶处皮下注射脂质体两性霉素B没有明显活性。游离药物在无毒剂量下无效。结果表明脂质体两性霉素B可能对治疗皮肤利什曼病有用。