Takemoto Koji, Yamamoto Yutaka, Ueda Yutaka, Kanazawa Katsunori, Yoshida Koichiro, Niki Yoshihito
Pharmacology Research Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Konohana-ku, Osaka, Japan.
Chemotherapy. 2009;55(2):105-13. doi: 10.1159/000194661. Epub 2009 Jan 19.
No clinical studies have compared the efficacy of liposomal formulation AMB (L-AMB) and voriconazole (VRC) in the treatment of pulmonary aspergillosis. The aim of this study was to compare the efficacy of L-AMB and VRC in murine pulmonary aspergillosis.
Leucopenic mice were infected intratracheally with Aspergillus fumigatus and treated intravenously with L-AMB (once a day) or VRC (twice a day).
L-AMB and VRC at a dose of >or=5 and >or=20 mg/kg, respectively, significantly prolonged the survival time of infected mice and reduced the pulmonary fungal burden in comparison with the control group. At the maximum recommended dose for clinical use, 5 mg/kg of L-AMB exhibited greater efficacy than 10 mg/kg of VRC, which achieved an area under the concentration-time curve level equivalent to that of 6 mg/kg (loading dose) in humans, in terms of increasing survival and reducing the fungal burden.
The in vivo efficacy of L-AMB was superior to that of VRC at the maximum recommended dose in a murine pulmonary aspergillosis model.
尚无临床研究比较脂质体制剂两性霉素B（L-AMB）和伏立康唑（VRC）治疗肺曲霉病的疗效。本研究旨在比较L-AMB和VRC在小鼠肺曲霉病中的疗效。
将白细胞减少的小鼠经气管内感染烟曲霉，并分别静脉注射L-AMB（每日一次）或VRC（每日两次）进行治疗。
与对照组相比，L-AMB剂量≥5mg/kg和VRC剂量≥20mg/kg时，显著延长了感染小鼠的存活时间，并减轻了肺部真菌负荷。在临床使用的最大推荐剂量下，就提高存活率和减轻真菌负荷而言，5mg/kg的L-AMB比10mg/kg的VRC疗效更佳，后者达到的浓度-时间曲线下面积水平相当于人类6mg/kg（负荷剂量）。
在小鼠肺曲霉病模型中，最大推荐剂量下L-AMB的体内疗效优于VRC。
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