Takemoto Koji, Yamamoto Yutaka, Ueda Yutaka, Sumita Yoshihiro, Yoshida Koichiro, Niki Yoshihito
Discovery Research Laboratories II, Sumitomo Pharmaceuticals Research Division, Konohana-ku, Osaka, Japan.
J Antimicrob Chemother. 2006 Apr;57(4):724-31. doi: 10.1093/jac/dkl005. Epub 2006 Jan 30.
The aim of this study was to evaluate the efficacy and tissue concentration of AmBisome and Fungizone in murine pulmonary aspergillosis, and to investigate the localization of AmBisome at the infection site.
Mice were infected intratracheally with Aspergillus fumigatus. A single dose of each of the antifungals was administered intravenously 4 h after infection. The efficacy of the antifungal treatment was assessed by the pulmonary fungal burden at 20 h post-treatment and the survival time over 1 month. The pulmonary amphotericin B (AMB) concentration was measured until 48 h after administration. The distribution of AmBisome in the lung was evaluated using rhodamine-labelled AmBisome and an anti-AMB antibody.
AmBisome at a dose of > or =1 mg/kg significantly prolonged the survival time of infected mice compared with the control group. At the maximum tolerated dose, 10 mg/kg AmBisome exhibited greater efficacy than 1 mg/kg Fungizone in terms of increasing survival and reducing the fungal burden. The pulmonary AMB concentration of 10 mg/kg AmBisome was higher than that of 1 mg/kg Fungizone. Tissue distribution analysis showed that AmBisome was localized at the infection site in the lung, and this might explain the potent in vivo efficacy in this infection model.
AmBisome is localized at the infection site in the lung and consequently may fully exhibit its in vivo activity. The efficacy of AmBisome is superior to that of Fungizone against pulmonary aspergillosis.
本研究旨在评估两性霉素B脂质体（AmBisome）和两性霉素B（Fungizone）在小鼠肺部曲霉病中的疗效及组织浓度，并研究AmBisome在感染部位的定位。
小鼠经气管内接种烟曲霉。感染后4小时静脉注射单剂量的每种抗真菌药物。通过治疗后20小时的肺部真菌负荷和1个月以上的生存时间评估抗真菌治疗的疗效。在给药后48小时内测量肺部两性霉素B（AMB）浓度。使用罗丹明标记的AmBisome和抗AMB抗体评估AmBisome在肺中的分布。
与对照组相比，剂量≥1mg/kg的AmBisome显著延长了感染小鼠的生存时间。在最大耐受剂量下，10mg/kg的AmBisome在提高生存率和降低真菌负荷方面比1mg/kg的Fungizone表现出更高的疗效。10mg/kg AmBisome的肺部AMB浓度高于1mg/kg Fungizone。组织分布分析表明，AmBisome定位于肺部感染部位，这可能解释了其在该感染模型中的强大体内疗效。
AmBisome定位于肺部感染部位，因此可能充分发挥其体内活性。AmBisome对肺部曲霉病的疗效优于Fungizone。
