目的 系统评价CYP2C19基因多态性对奥美拉唑药物代谢动力学的影响。方法 计算机检索截止至2012年2月的Cochrane、PubMed、Embase、CNKI等数据库,收集有关CYP2C19基因多态性对奥美拉唑药动学影响的研究。用RevMan5.1软件对符合纳入标准的研究进行Meta分析。结果 共纳入12篇回顾性研究。其中英文8篇,中文4篇。Meta分析结果表明,CYP2C19基因多态性显著影响ρmax、AUC、t1/2和CL/F。PM基因型组的ρmax、AUC和t1/2的值均大于HEM基因型组,且HEM基因型组均显著大于EM基因型组;基因型为EM人群的CL/F显著大于HEM基因型组,HEM人群的CL/F也显著大于HM基因型组。结论 CYP2C19基因多态性显著影响奥美拉唑的体内代谢,但其代谢还受多种其他因素影响,尚需高质量大样本量的前瞻性研究来证实。
Abstract
Objective To evaluate the influence of CYP2C19 genetic polymorphism on omeprazole pharmacokinetics. METHODS Cochrane library,PubMed,Embase and CNKI databases were searched for trials investigating the influence of CYP2C19 genetic polymorphism on omeprazole pharmacokinetics reported before February 2012. Meta-analysis was performed by RevMan 5.1 software. RESULTS Twelve retrospective studies,eight in English and four in Chinese,were included. Meta-analysis showed that CYP2C19 polymorphism significantly influenced the ρmax,AUC,t1/2 and CL/F. The ρmax,AUC,t1/2 and CL/F in PM genotype group were higher than those in HEM group,and those in HEM group were significantly higher than in EM group. And the CL/F in EM group was significantly higher than that in HEM group followed by that in PM group. CONCLUSION CYP2C19 genetic polymorphism affects omeprazole exposure significantly,but there are still other influencing factors. Large prospective studies are needed.
关键词
奥美拉唑 /
细胞色素P4502C19 /
基因多态性
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Key words
omeprazole /
CYP2C19 /
genetic polymorphism
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中图分类号：
R975.6
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参考文献
[1] ZHOU X Q,DUAN L F,ZHANG Y, et al. Advance of CYP2C19 polymorphism on clinical efficacy of omeprazole. Chin J Drug Applica Monit（中国药物应用与监测）,2010,7(1): 55-57.
[2] PENG R G,WANG Q. Drug interactions between omeprazole and CYP2C19 genetic polymorphism. J Luzhou Med Coll（泸州医学院学报）,2010,33(6): 718-720.
[3] CHOWBAY B,LI H,DAVID M,et al. Meta-analysis of the influence of MDR1 C3435T polymorphism on digoxin pharmacokinetics and MDR1 gene expression. Br J Clin Pharmacol,2005,60(2):159-171.
[4] HUNFELD N G,MATHOT R A,TOUW D J,et al. Effect of CYP2C19*2 and *17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians. Br J Clin Pharmacol,2008,65(5):752-760.
[5] YASUI-FURUKORI N,TAKENORIT,NAKAGAMI T,et al. Different inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes. British J Clinical Pharm,2004,57（4）:487-494.
[6] BALDWIN R M,OHLSSON S,PEDERSEN R S, et al.Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; A pharmacokinetic study in healthy volunteers. Br J Clin Pharmacol,2008,65(5):767-774.
[7] YIN O Q,TOMLINSON B,CHOW A H, et al. Omeprazole as a CYP2C19 marker in Chinese subjects: Assessment of its gene-doseeffect and intrasubjectvariability. J Clin Pharmacol,2004,44(6):582-589.
[8] SHIRAI N,FURUTA T,MORIYAMA Y, et al. Effects of CYP2C19 genotypic differences in the metabolism of omeprazole andrabeprazole on intragastric pH. Aliment Pharmacol Ther,2001,15(12):1929-1937.
[9] KITA T,SAKAEDA T,AOYAMA N, et al.Optimal dose of omeprazole for CYP2C19 extensive metabolizers in anti-Helicobacter pylori therapy: Pharmacokinetic considerations. Biol Pharm Bull,2002,25(7):923-927.
[10] CHO J Y,YU K S,JANG I J, et al.Omeprazole hydroxylation is inhibited by a single dose of moclobemide in homozygotic EM genotype for CYP2C19. Br J Clin Pharmacol,2002,53(4):393-397.
[11] MA J J,LI J H,CAO X M,et al. The influence of CYP2C19 genotype on omeprazole pharmacokinetics and relative bioavailability. Chin Pharmacol Bull（中国药理学通报）,2010,26(2): 258-262.
[12] HU X P,XU J M,HU Y M, et al. The influence of CYP2C19 genotype on omeprazole pharmacokinetics and relative bioavailability. Chin Pharmacol Bull（中国药理学通报）,2005,21(10): 1210-1213.
[13] FU L Q,HUANG F,WU D Z,et al. Pharmacokinetic comparison of omeprazole and its metabolites between Chinese CYP2C19 Ems and PMs subjects. Chin Pharm J（中国药学杂志）,2004,39(8): 614-616.
[14] HU Y M,XU J M. Effects of CYP2C19 genetic polymorphism on the pharmacokinetics and pharmacodynamics of rebeprazole and omeprazole in Chinese subjects . Hefei: Anhui Medical University（安徽医科大学）,2005.
[15] YANG Y X,LEWID J D,EPSTEIN S,et al. Long-term proton pumpinhibitor therapy and risk of hip fracture. JAMA,2006,296(24): 2947-2953.
[16] WANG L J,TANG H L,DUAN J L. Influence of CYP2C19 genetic polymorphisms on voriconazole pharmacokinetics: A systematic review. Chin J Clin Pharmacol（临床药理学杂志）,2011,27(8):607-611.
BALDWIN R M,OHLSSON S,PEDERSEN R S,et al. Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; A pharmacokinetic study in healthy volunteers. Br J Clin Pharmacol,2008,65(5):767-774.
[17] HUNFELD N G,MATHOT R A,TOUW D J,et al. Effect of CYP2C19*2 and *17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians.Br J Clin Pharmacol, 2008,65(5):752-760.
[18] FURUTA T,OHASHI K,KOSUGE K, et al. CYP2C19 Genetype status and effect of omeprazole on intragastric pH in humans. Clin Pharmacol Ther,1999,65（5）:552-561.
[19] FURUTA T,SHIRAI N,SUGIMOTO M, et al. Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies . Drug Metab Pharmacokkinet,2005,20（3）:153-167.
[20] ISHIZAKI T,HORAI Y. Review article: Cytochrome P450 and the metabolism of proton pump inhibitors-emphasis on rabeprazole. Aliment Pharmacol Ther,1999,13(3):27-36.
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脚注
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基金
广东省部产学研合作引导项目(2010B090400081);佛山市高明区科技三项费用项目(201015)
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