左奥硝唑等4种抗菌药的防耐药突变浓度测定及临床用药剂量合理性的分析  

The Resistant Mutant Prevention Concentrations Determination of Levornidazole and Other Three Related Drugs and Analysis to Suitability of These Drug′s Dosage in Clinic

作　　者：汪辉[1] 郝琨[2] 王广基[2] 

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009 [2]中国药科大学药物代谢动力学重点实验室,江苏南京210009

出　　处：《药学进展》2012年第6期277-281,共5页Progress in Pharmaceutical Sciences

基　　金：国家"重大新药创制"科技重大专项(No.2008ZX09101-101);江苏省科技成果转化专项(No.BA2010027)

摘　　要：目的:测定左奥硝唑、亚胺培南西司他丁钠、莫西沙星和替硝唑单用或联用时的防耐药突变浓度,为临床上的合理用药提供依据。方法:选用体外脆弱拟杆菌ATCC25285,分别以微量肉汤稀释法测定供试药物的体外最低抑菌浓度;棋盘格法测定分级抑菌浓度指数;平板法测定单独用药及联合用药后的防耐药突变浓度。分析比较各药防耐药突变浓度与体内最大血药浓度之间的关系。结果:左奥硝唑、亚胺培南西司他丁钠、莫西沙星和替硝唑单独使用时对脆弱拟杆菌ATCC25285的防耐药突变浓度分别为10.24、5.12、4.0和20.24 mg.L-1;按临床目前使用的常规剂量,各药的体内最大血药浓度与其防耐药突变浓度之比分别为1.82、2.73～4.69、0.75～1.0和0.684～1.02;而左奥硝唑与莫西沙星、亚胺培南西司他丁钠联用后的防耐药突变浓度分别降低为3.2和1.6 mg.L-1,联用后的FIC分别为0.75和0.5。表明左奥硝唑与莫西沙星、亚胺培南西司他丁钠联用可明显缩小各自的防耐药突变浓度。结论:左奥硝唑在目前的常规剂量下,不易引起耐药性,但替硝唑的剂量应予适当增加。左奥硝唑与莫西沙星、亚胺培南西司他丁钠联用有助于减少耐药性。Objective： The resistant mutant prevention concentrations （MPCs） of levornidazole, imipenem and cilastatin sodium, moxifloxacin and tinidazole on single use or on combined use were determined to provide references for clinical treatments. Methods： Bacteroides Minimum inhibitory concentration（MIC）, fractional inhibitory determined by broth dilution, checkerboard and agar plate levornidazole, imipenem and cilastatin sodium, moxifloxacin fragilis ATCC25285 was used in this study. concentration（FIC） indices and MPCs were method, respectively. Results： The MPC of and tinidazole on single use was 10. 24,5.12, 4. 0 and 20. 24 mg.L-1, respectively. The ratio of Cmax to MPC of levornidazole, imipenem and cilastatin sodium, moxifloxaein and tinidazole on single use was 1.82, 2.73- 4. 69,0. 75-1.0 and 0. 684- 1.02, respectively. MPCs of levornidazole combined with moxifloxacin or imipenem and eilastatin sodium was 3.2 mg. L - 1 with FIC of 0. 75 and 1.6 mg. L- 1 with FIC of 0. 5. It was shown that the combination of levornidazole and moxifloxacin or imipenem and eilastatin sodium can significantly reduce the MPC of drugs. Conclusions： The rate of resistance can be decreased by levornidazole combined with moxifloxacin or imipenem and cilastatin sodium. The dosage of levoruidazole in clinic was suitable, but dosage of tinidazole may be increased.

关 键 词：左奥硝唑 莫西沙星 亚胺培南西司他丁钠 替硝唑 防耐药突变浓度 给药剂量 

分 类 号：R96[医药卫生—药理学]