LYRM03联合多黏菌素B治疗小鼠肺炎克雷伯菌肺炎的药效学研究  

In vivo pharmacodynamics of the combination of LYRM03 and polymyxin B in a murine lung infection model caused by Klebsiella pneumoniae

作　　者：李鑫 施思 戈梅 冯美卿[2] 赵旭 郭蓓宁 张菁 Li Xin;Shi Si;Ge Mei;Feng Mei-qing;Zhao Xu;Guo Bei-ning;Zhang Jing(Institute of Antibiotics, Huashan Hospital, Fudan University, Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai 200040;Department of Microbiology ＆ Biochemical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203;Shanghai Laiyi Center for Biopharmaceutical R ＆ D, Shanghai 201203)

机构地区：[1]复旦大学附属华山医院抗生素研究所卫生部抗生素临床药理重点实验室,上海200040 [2]复旦大学药学院微生物与生化药学,上海201203 [3]上海来益生物药物研究开发中心有限责任公司,上海201203

出　　处：《中国抗生素杂志》2018年第6期772-776,F0003,共6页Chinese Journal of Antibiotics

基　　金：国家自然科学基金面上项目(No.81373494);上海市科委实验动物研究专项基金(No.15140903300)

摘　　要：目的将新化合物LYRM03和多黏菌素B联合用于治疗小鼠肺炎,拟观察在达到同等治疗效果的情况下,联合LYRM03是否能够降低多黏菌素B的用量。方法采用耳窥镜直视下气管插管法建立小鼠肺炎模型,采用多黏菌素B单药或联合LYRM03的不同给药方案进行治疗,观察期96h,从小鼠存活率、体重变化、活动度评分、肺组织细菌载量等指标比较两者的治疗效果。结果高剂量多黏菌素B治疗组疗效明显优于低剂量组,但单药与联合用药间无明显差别。多黏菌素B按1和5mg/kg单药治疗组存活率分别为50%和100%,联合用药后存活率分别为50%和83.3%。单药与联合用药治疗后两组间其余各项观察指标也无显著性差异。结论联合LYRM03与多黏菌素B单药治疗相比,疗效没有明显差异,提示联合LYRM03不能降低多黏菌素B的用量。Objective To examine whether the dose of polymyxin B can be reduced when combined with LYRM03 in a murine lung infection model. Methods A murine lung infection model caused by Klebsiella pneumoniae was established through a new inoculation method with an otoscope. Pharmacodynamics studies were performed following the administration of polymyxin B monotherapy or combined with LYRM03. The survival rate, weights, activity scores and bacteria loads in lungs over 96h of the groups were observed to compare the therapeutic effects. Results The survival rates of the 1 and 5mg/kg polymyxin B groups were 50% and 100%, which were 50% and 83.3% when combined with LYRM03. There were no significant differences in survival rates as well as other indicators between the monotherapy group and the combination therapy group. Conclusion There was no significant difference in therapeutic effect between the monotherapy and the corresponding combination therapy group, indicating that the therapy dose ofpolymyxin B cannot be reduced when combined with LYRM03.

关 键 词：药效学 LYRM03 多黏菌素B 联合治疗 免疫调节 小鼠肺炎模型 

分 类 号：R978.1[医药卫生—药品]