有机阳离子转运体2(808G>T)基因多态性对健康受试者体内盐酸二甲双胍药动学影响的Meta分析
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摘要
目的:系统评价有机阳离子转运体2[(OCT2)808G>T]基因多态性对健康受试者体内盐酸二甲双胍药动学的影响,以为临床用药提供循证参考。方法:计算机检索Pub Med、EMBase、西文生物医学期刊文献数据库、中国期刊全文数据库、中文科技期刊数据库、万方数据库,收集(OCT2)808G>T基因多态性对健康受试者体内盐酸二甲双胍药动学影响的相关研究,采用Rev Man 5.1统计软件进行Meta分析。结果:共纳入5项回顾性研究,合计172例受试者,基因检测结果为GT型、TT型、GG型。Meta分析结果表明,与GT型基因相比较,TT型会延长盐酸二甲双胍的半衰期;与TT型基因相比较,GG型会增大盐酸二甲双胍的峰浓度。而(OCT2)808G>T基因多态性不会对肾脏清除率、肌酐清除率和药-时曲线下面积造成影响。结论:(OCT2)808G>T基因多态性对健康受试者体内盐酸二甲双胍半衰期和峰浓度有一定影响,对肾脏清除率、肌酐清除率和药-时曲线下面积没有影响。受纳入研究方法学的限制,该结论尚需大样本、高质量的研究进一步验证。
OBJECTIVE:To systematically review the effect of organic cation transporter 2 [(OCT2)808G>T] gene polymorphism on the metformin hydrochloride pharmacokinetics in vivo,and to provide evidence-based reference for clinical medication.METHODS:Retrieved from Pub Med,EMBase,Foreign Medical Journey Service,CJFD,VIP database and Wanfang database,related studies about the effect of(OCT2)808G>T gene polymorphism on the metformin hydrochloride pharmacokinetics in vivo were collected,and Meta-analysis was performed by using Rev Man 5.1 statistics software.RESULTS:A total of 5 retrospective studies were included,involving 172 patients.The result of gene type was type GT,type TT and type GG.Results of Meta-analysis showed,compared with type GT volunteers,type TT could prolong the half-time period of metformin hydrochloride;compared with type TT,type GG could increase the peak concentration.However,(OCT2)808G>T gene polymorphism had no effects on the renal clearance rate,creatinine clearance rate and area under the drug-time curve.CONCLUSIONS:(OCT2)808G>T gene polymorphism has certain effect on the half-time period and peak concentration of metformin hydrochloride in vivo of health volunteer,and has no effect on the renal clearance rate,creatinine clearance rate and area under the drug-time curve.Due to the limit of research methodological quality,large-scale and high quality studies are required for further validation of the conclusions.KEYWRODS Diabetes;Metformin;Gene polymorphism;Organic cation transporter 2
OBJECTIVE:To systematically review the effect of organic cation transporter 2 [(OCT2)808G>T] gene polymorphism on the metformin hydrochloride pharmacokinetics in vivo,and to provide evidence-based reference for clinical medication.METHODS:Retrieved from Pub Med,EMBase,Foreign Medical Journey Service,CJFD,VIP database and Wanfang database,related studies about the effect of(OCT2)808G>T gene polymorphism on the metformin hydrochloride pharmacokinetics in vivo were collected,and Meta-analysis was performed by using Rev Man 5.1 statistics software.RESULTS:A total of 5 retrospective studies were included,involving 172 patients.The result of gene type was type GT,type TT and type GG.Results of Meta-analysis showed,compared with type GT volunteers,type TT could prolong the half-time period of metformin hydrochloride;compared with type TT,type GG could increase the peak concentration.However,(OCT2)808G>T gene polymorphism had no effects on the renal clearance rate,creatinine clearance rate and area under the drug-time curve.CONCLUSIONS:(OCT2)808G>T gene polymorphism has certain effect on the half-time period and peak concentration of metformin hydrochloride in vivo of health volunteer,and has no effect on the renal clearance rate,creatinine clearance rate and area under the drug-time curve.Due to the limit of research methodological quality,large-scale and high quality studies are required for further validation of the conclusions.KEYWRODS Diabetes;Metformin;Gene polymorphism;Organic cation transporter 2
引文
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[5]Kimura N,Masuda S,Tanihara Y,et al.Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1[J].Drug Metab Pharmacok,2005,20(5):379.
[6]Kimura N,Okuda M,Inui KI.Metformin transport by renal basolateral organic cation transporter OCT2[J].Pharm Res,2005,22(2):255.
[7]Wang DS,Jonker JW,Kato Y,et al.Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin[J].J Pharmacol Exp Ther,2002,302(2):510.
[8]Wang DS,Kusuhara H,Kato Y,et al.Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin[J].Mol Pharmacol,2003,63(4):844.
[9]Shu Y,Sheardown SA,Brown C,et al.Effect of genetic variation in the organic cation transporter 1(OCT1)on metformin action[J].J Clin Invest,2007,117(5):1 422.
[10]陈丹丹.人类有机阳离子转运体2(OCT2)808G>T对健康受试者体内盐酸二甲双胍药代动力学和药效学的影响[D].长沙:中南大学.2008.
[11]Song IS,Shin HJ,Shim EJ,et al.Genetic variants of the organic cation transporter 2 influence the disposition of metformin[J].Clin Pharmaco Ther,2008,84(5),559.
[12]Wang ZJ,Yin OQ,Tomlinson B,et al.OCT2 polymorphisms and in-vivo renal functional consequence:studies with metformin and cimetidine[J].Pharmacogenet Genom,2008,18(7),637.
[13]Chen Y,Li S,Brown C,et al.Effect of genetic variation in the organic cation transporter 2(OCT2),on the renal elimination of metformin[J].Pharmacogenet Genom,2009,9(7):497.
[14]Yoon H,Cho HY,Yoo HD,et al.Influences of organic cation transporter polymorphisms on the population pharmacokinetics of metformin in healthy subjects[J].Aaps J,2013,15(2):571.
[2]Melchior WR,Jaber LA.Metformin:an antihyperglycemic agent for treatment of typeⅡdiabetes[J].Ann Pharmacother,1996,30(2),158.
[3]Hundal RS,Krssak M,Dufour S,et al.Mechanism by which metformin reduces glucose production in type 2 diabetes[J].Diabetes,2000,49(12):2 063.
[4]Reitman ML.Pharmacogenetics of metformin response:a step in the path toward personalized medicine[J].J Clin Invest,2007,117(5):1 226.
[5]Kimura N,Masuda S,Tanihara Y,et al.Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCT1[J].Drug Metab Pharmacok,2005,20(5):379.
[6]Kimura N,Okuda M,Inui KI.Metformin transport by renal basolateral organic cation transporter OCT2[J].Pharm Res,2005,22(2):255.
[7]Wang DS,Jonker JW,Kato Y,et al.Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin[J].J Pharmacol Exp Ther,2002,302(2):510.
[8]Wang DS,Kusuhara H,Kato Y,et al.Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin[J].Mol Pharmacol,2003,63(4):844.
[9]Shu Y,Sheardown SA,Brown C,et al.Effect of genetic variation in the organic cation transporter 1(OCT1)on metformin action[J].J Clin Invest,2007,117(5):1 422.
[10]陈丹丹.人类有机阳离子转运体2(OCT2)808G>T对健康受试者体内盐酸二甲双胍药代动力学和药效学的影响[D].长沙:中南大学.2008.
[11]Song IS,Shin HJ,Shim EJ,et al.Genetic variants of the organic cation transporter 2 influence the disposition of metformin[J].Clin Pharmaco Ther,2008,84(5),559.
[12]Wang ZJ,Yin OQ,Tomlinson B,et al.OCT2 polymorphisms and in-vivo renal functional consequence:studies with metformin and cimetidine[J].Pharmacogenet Genom,2008,18(7),637.
[13]Chen Y,Li S,Brown C,et al.Effect of genetic variation in the organic cation transporter 2(OCT2),on the renal elimination of metformin[J].Pharmacogenet Genom,2009,9(7):497.
[14]Yoon H,Cho HY,Yoo HD,et al.Influences of organic cation transporter polymorphisms on the population pharmacokinetics of metformin in healthy subjects[J].Aaps J,2013,15(2):571.