Comparative study on the efficacy of AmBisome and Fungizone in a mouse model of pulmonary aspergillosis.
Comparative study on the efficacy of AmBisome and Fungizone in a mouse model of pulmonary aspergillosis.
复制标题
AmBisome 和 Fungizone 在小鼠肺曲霉病模型中的疗效比较研究。
DOI：
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发表时间：
2006
影响因子：
5.2
通讯作者：
Y. Niki
中科院分区：
文献类型：
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作者：
K. Takemoto;Yutaka Yamamoto;Y. Ueda;Y. Sumita;Koichiro Yoshida;Y. Niki
目标
本研究的目的是评价AmBisome和Fungizone对小鼠肺曲霉病的疗效和组织浓度，并研究AmBisome在感染部位的定位。
方法
小鼠经气管内感染烟曲霉菌。感染后4 h静脉内给予单剂量的每种抗真菌药。根据治疗后20 h肺部真菌负荷和1个月以上生存时间评价抗真菌治疗的疗效。给药后48 h测定肺组织AMB浓度。使用罗丹明标记的AmBisome和抗AMB抗体评价AmBisome在肺中的分布。
结果
与对照组相比，剂量≥ 1 mg/kg的AmBisome显著延长了感染小鼠的存活时间。在最大耐受剂量下，10 mg/kg AmBisome在增加存活率和降低真菌负荷方面表现出比1 mg/kg Fungizone更大的功效。10 mg/kg AmBisome组的肺AMB浓度高于1 mg/kg Fungizone组。组织分布分析显示AmBisome定位于肺中的感染部位，并且这可以解释在该感染模型中的有效体内功效。
结论
AmBisome定位于肺中的感染部位，因此可以充分显示其体内活性。AmBisome对肺曲霉病的疗效上级优于两性霉素B。
OBJECTIVES
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.