Otsubo T, Maruyama K, Maesaki S, Miyazaki Y, Tanaka E, Takizawa T, Moribe K, Tomono K, Tashiro T, Kohno S
Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
Antimicrob Agents Chemother. 1998 Jan;42(1):40-4. doi: 10.1128/AAC.42.1.40.
We investigated the efficacy of long-circulating immunoliposomal amphotericin B (AmB) against invasive pulmonary aspergillosis in mice using three types of liposomal AmB: conventional liposomal AmB (AmBisome), a long-circulating liposomal AmB and prepared by coating the liposome surface with polyethylene glycol (PEG; PEG-L-AmB), long-circulating immunoliposomal AmB (34A-PEG-L-AmB). The survival rates for mice with invasive pulmonary aspergillosis treated with an intravenous dose of 2 mg of AmBisome, PEG-L-AmB, or 34A-PEG-L-AmB per kg of body weight were 16.7, 83.3, and 100%, respectively. Treatment with 34A-PEG-L-AmB produced a marked reduction in the number of Aspergillus fumigatus organisms in the lungs. Pharmacokinetic studies showed the presence of high AmB concentrations in the plasma of mice treated with PEG-L-AmB (40.8 microg/ml) and in the lungs of mice treated with 34A-PEG-L-AmB (42.3 microg/g). We conclude that 34A-PEG-L-AmB, a long-circulating immunoliposomal AmB, is a promising form of AmB against invasive pulmonary aspergillosis.
我们使用三种类型的脂质体两性霉素B研究了长循环免疫脂质体两性霉素B（AmB）对小鼠侵袭性肺曲霉病的疗效：常规脂质体两性霉素B（安必素）、通过用聚乙二醇（PEG；PEG-L-AmB）包被脂质体表面制备的长循环脂质体两性霉素B、长循环免疫脂质体两性霉素B（34A-PEG-L-AmB）。每千克体重静脉注射2毫克安必素、PEG-L-AmB或34A-PEG-L-AmB治疗侵袭性肺曲霉病小鼠的存活率分别为16.7%、83.3%和100%。用34A-PEG-L-AmB治疗可使肺部烟曲霉菌数量显著减少。药代动力学研究表明，用PEG-L-AmB治疗的小鼠血浆中存在高浓度的AmB（40.8微克/毫升），用34A-PEG-L-AmB治疗的小鼠肺部存在高浓度的AmB（42.3微克/克）。我们得出结论，长循环免疫脂质体两性霉素B 34A-PEG-L-AmB是一种有前景的用于治疗侵袭性肺曲霉病的AmB剂型。
