Fohrer Cécile, Nivoix Yasmine, Moulin Jean-Charles, Marçais Ambroise, Herbrecht Raoul
Département d'Hématologie et d'Oncologie, Hôpital de Hautepierre, Strasbourg, France.
Therapie. 2006 May-Jun;61(3):235-42. doi: 10.2515/therapie:2006047.
Three lipid formulations of amphotericin B have been developed: amphotericin B colloidal dispersion, amphotericin B lipid complex, and liposomal amphotericin B. These three compounds differ by their lipid composition and therefore by their physical characteristics, their pharmacokinetics, and their safety and efficacy profile. There is a consensus to accept reduced toxicity of these formulations, especially reduced, but not absence of, renal toxicity as compared to amphotericin B deoxycholate. Few well-designed studies have been conducted and none of them demonstrated convincingly superiority in term of efficacy of any of the lipid preparations over amphotericin B deoxycholate. Recently a double blind randomized study compared a standard dose of 3 mg/kg/d of liposomal amphotericin B and a loading dose (10 mg/kg/d for 14 days and then the standard dose) in primary therapy of invasive filamentous fungal infections, mainly aspergillosis. Response rate at end of randomized therapy as well as survival at 12 weeks was numerically superior in the standard dose arm but this difference was not statistically significant. Lack of benefit of high dose liposomal amphotericin B in aspergillosis cannot yet be extrapolated to other filamentous fungal infections. Nephrotoxicity was substantially higher in the loading dose arm and this contraindicates its use in clinical practice.
两性霉素B已开发出三种脂质制剂：两性霉素B胶体分散体、两性霉素B脂质复合物和脂质体两性霉素B。这三种化合物因其脂质组成不同，因而在物理特性、药代动力学以及安全性和有效性方面存在差异。人们普遍认为这些制剂的毒性有所降低，尤其是与两性霉素B脱氧胆酸盐相比，肾毒性降低，但并非完全没有。很少有设计良好的研究，而且没有一项研究令人信服地证明任何一种脂质制剂在疗效方面优于两性霉素B脱氧胆酸盐。最近一项双盲随机研究比较了3mg/kg/d的标准剂量脂质体两性霉素B和负荷剂量（10mg/kg/d，共14天，然后是标准剂量）在侵袭性丝状真菌感染（主要是曲霉病）初始治疗中的效果。随机治疗结束时的缓解率以及12周时的生存率在标准剂量组在数值上更高，但这种差异无统计学意义。高剂量脂质体两性霉素B在曲霉病中未显示出益处，这一点尚不能外推至其他丝状真菌感染。负荷剂量组的肾毒性显著更高，这表明其在临床实践中不宜使用。
