细胞色素P450 2C9基因多态性对格列美脲药代动力学影响的Meta分析  

Meta-analysis of the effect of cytochrome P450 2C9 gene polymorphism on the pharmacokinetics of glimepiride

作　　者：贾晓娜 张晓丹[1] 周双[1] 刘雄飞 赵侠[1] 周颖[1] 崔一民[1] JIA Xiao-na;ZHANG Xiao-dan;ZHOU Shuang;LIU Xiong-fei;ZHAO Xia;ZHOU Ying;CUI Yi-min(Department of Pharmacy,Peking University First Hospital,Beijing 100034, China;Department of Pharmacy Administration and Clinical Pharmacy, Peking University Health Science Center, Beijing 100191,China;School of Basic medicine and Clinical pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]北京大学第一医院药剂科,北京100034 [2]北京大学医学部药事管理与临床药学系,北京100191 [3]中国药科大学基础医学与临床药学院,南京211198

出　　处：《中国临床药理学杂志》2019年第2期173-176,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家科技重大专项--重大新药创制资助项目(2017ZX09101001)

摘　　要：目的用Meta分析评价细胞色素P450 2C9(CYP2C9)基因多态性对格列美脲的药代动力学的影响。方法用计算机检索PubMed、EMbase、Cochrane Library、Web of Science、中国知网和万方数据库,收集有关CYP2C9基因多态性与格列美脲药代动力学关系的研究,提取血药浓度-时间曲线下面积(AUC)、峰浓度(C_(max))、清除率(CL/F)和半衰期(t_(1/2))等药代动力学参数,用RevMan 5. 3软件对纳入的研究进行Meta分析。结果最终共纳入3篇文献进行Meta分析,共70例病例。CYP2C9~*1~*3突变型与CYP2C9~*1~*1野生型相比,AUC[463. 19(275. 28,651. 11)]和C_(max)[43. 02(1. 86,84. 17)]差异均有统计学意义(均P <0. 05),但CL/F[-1. 42(-3. 10,0. 25)]和t_(1/2)[2. 91(-4. 69,10. 52)]差异均无统计学意义(均P> 0. 05)。结论 CYP2C9*3基因多态性对格列美脲的药代动力学存在影响,CYP2C9~*1~*3突变型人群的格列美脲突变型人群格列美脲的系统暴露参数AUC、C_(max)均增大、CL/F减小,代谢减慢,对临床用药的安全性和有效性有一定的借鉴意义。Objective To evaluate the effect of cytochrome P450 2C9( CYP2C9) polymorphism on pharmacokinetics of glimepiride by Meta-analysis. Methods The PubMed,EMbase,Cochrane Library,Web of Science,CNKI,and Wanfang Database were searched to collect researches on the relationship between CYP2C9 gene polymorphism and glimepiride pharmacokinetics. The pharmacokinetic parameters such as area under the blood concentration-time curve( AUC),peak concentration( Cmax),clearance rate( CL/F) and half-life( t1/2) were extracted. RevMan 5. 3 software was used to analyze the included studies.Results Three articles were included for Meta-analysis,and a total of 70 cases were included. Compared with CYP2 C9* 1* 1 wild type,CYP2 C9*1*3 mutant had statistically significant differences in AUC[463. 19( 275. 28,651. 11) ]and Cmax[43. 02( 1. 86,84. 17) ]( both P < 0. 05). However,there were no significant differences in CL/F[-1. 42(-3. 10,0. 25) ] and t1/2[2. 91(-4. 69,10. 52) ]( both P > 0. 05). Conclusion The CYP2 C9*3 gene polymorphism has an effect on the pharmacokinetics of glimepiride. The CYP2 C9* 1* 3 mutant population has a higher Cmaxand AUC, and lower CL/F ofglimepiride,which has some implications for clinical use.

关 键 词：格列美脲 细胞色素P450 2C9 基因多态性 药代动力学 META分析 

分 类 号：R977.15[医药卫生—药品]