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
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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( C_(max)),clearance rate( CL/F) and half-life( t_(1/2)) 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 C_(max)[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 t_(1/2)[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 C_(max)and AUC, and lower CL/F ofglimepiride,which has some implications for clinical use.
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( C_(max)),clearance rate( CL/F) and half-life( t_(1/2)) 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 C_(max)[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 t_(1/2)[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 C_(max)and AUC, and lower CL/F ofglimepiride,which has some implications for clinical use.
引文
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[10]WANG R,CHEN K,WEN S Y,et al.Pharmacokinetics of glimepiride and cytochrome P450 2C9 genetic polymorphisms[J].Clin Pharmacol Ther,2005,78(1):90-92.
[11]SUZUKI K,YANAGAWA T,SHIBASAKI T,et al.Effect of CYP2C9 genetic polymorphisms on the efficacy and pharmacokinetics of glimepiride in subjects with type 2 diabetes[J].Diabetes Res Clin Pract,2006,72(2):148-154.
[12]陈騉.中国人群P450 2C9基因多态性与磺脲类药物代谢的关系[D].青岛:中国海洋大学,2005.
[13]RAGIA G,PETRIDIS I,TAVRIDOU A,et al.Presence of CYP2C9*3 allele increases risk for hypoglycemia in type 2 diabetic patients treated with sulfonylureas[J].Pharmacogenomics,2009,10(11):1781-1787.
[2]KIRCHHEINER J,MEINEKE I,MULLER G,et al.Influence of CYP2C9 and CYP2D6 polymorphisms on the pharmacokinetics of nateglinide in genotyped healthy volunteers[J].Clin Pharmacokinet,2004,43(4):267-278.
[3]李赟,何芳,曾彩雯,等.CYP2C9、CYP2C19、CYP3A4基因多态性对磺脲类降糖药代谢的影响[J].中国临床药理学与治疗学,2012,17(5):582-587.
[4]XIE H G,PRASAD H C,KIM R B,et al.CYP2C9 allelic variants:ethnic distribution and functional significance[J].Adv Drug Deliv Rev,2002,54(10):1257-1270.
[5]曾宪涛,刘慧,陈曦,等.Meta分析系列之四:观察性研究的质量评价工具[J].中国循证心血管医学杂志,2012,4(4):297-299.
[6]CHOWBAY B,LI H,DAVID M,et al.Meta-analysis of the influence of MDR1 C3435T polymorphism on digoxin pharmacokinetics and MDR1 gene expression[J].Br J Clin Pharmacol,2005,60(2):159-171.
[7]LEE H W,LIM M S,LEE J,et al.Frequency of CYP2C9 variant alleles,including CYP2C9*13 in a Korean population and effect on glimepiride pharmacokinetics[J].J Clin Pharm Ther,2012,37(1):105-111.
[8]YOO H D,KIM M S,CHO H Y,et al.Population pharmacokinetic analysis of glimepiride with CYP2C9 genetic polymorphism in healthy Korean subjects[J].Eur J Clin Pharmacol,2011,67(9):889-898.
[9]CHO H J,LEE S Y,KIM Y G,et al.Effect of genetic polymorphisms on the pharmacokinetics and efficacy of glimepiride in a Korean population[J].Clin Chim Acta,2011,412(19-20):1831-1834.
[10]WANG R,CHEN K,WEN S Y,et al.Pharmacokinetics of glimepiride and cytochrome P450 2C9 genetic polymorphisms[J].Clin Pharmacol Ther,2005,78(1):90-92.
[11]SUZUKI K,YANAGAWA T,SHIBASAKI T,et al.Effect of CYP2C9 genetic polymorphisms on the efficacy and pharmacokinetics of glimepiride in subjects with type 2 diabetes[J].Diabetes Res Clin Pract,2006,72(2):148-154.
[12]陈騉.中国人群P450 2C9基因多态性与磺脲类药物代谢的关系[D].青岛:中国海洋大学,2005.
[13]RAGIA G,PETRIDIS I,TAVRIDOU A,et al.Presence of CYP2C9*3 allele increases risk for hypoglycemia in type 2 diabetic patients treated with sulfonylureas[J].Pharmacogenomics,2009,10(11):1781-1787.