CAJ | 학술논문

目的：探讨有机阳离子转运体1（OCT1）基因中 rs2282143（P341L ，1022C＞ T）、rs628031（M408V ，1222A＞G）和rs36056065（ins/del GTAAGTTG）多态性对二甲双胍药代动力学的影响。方法65例男性健康自愿者空腹口服盐酸二甲双胍片500 mg ，采用液相色谱-串联质谱法测定血浆中二甲双胍的浓度，并根据rs2282143、rs628031和rs36056065多态性进行分组。结果 rs2282143多态性中CC、C T 和 T T分别为45例（69．2％）、19例（29．2％）和1例（1．5％），CC 和 CT 组间的 Cmax 、Tmax 、AUC0-t 、AUC0-∞和 T1/2差异无统计学意义（P＞0．05）。rs628031与rs36056065等位基因完全连锁，其中 AA/ins、AG/ins-del 和 GG/del 分别为8例（12．3％）、24例（36．9％）和33例（50．8％）。AG/ins-del的Cmax 、AUC0-t 、AUC0-∞显著高于 AA/ins和GG/del ，差异有统计学意义（P＜0．05），AA/ins和GG/del之间差异无统计学意义（P＞0．05）；Tmax 、T1/2在3种基因型间差异无统计学意义（P＞0．05）。结论 rs2282143多态性与二甲双胍药代动力学无相关性，完全连锁的 rs628031和 rs36056065与二甲双胍药代动力学密切相关。
목적：탐토유궤양리자전운체1（OCT1）기인중 rs2282143（P341L ，1022C＞ T）、rs628031（M408V ，1222A＞G）화rs36056065（ins/del GTAAGTTG）다태성대이갑쌍고약대동역학적영향。방법65례남성건강자원자공복구복염산이갑쌍고편500 mg ，채용액상색보-천련질보법측정혈장중이갑쌍고적농도，병근거rs2282143、rs628031화rs36056065다태성진행분조。결과 rs2282143다태성중CC、C T 화 T T분별위45례（69．2％）、19례（29．2％）화1례（1．5％），CC 화 CT 조간적 Cmax 、Tmax 、AUC0-t 、AUC0-∞화 T1/2차이무통계학의의（P＞0．05）。rs628031여rs36056065등위기인완전련쇄，기중 AA/ins、AG/ins-del 화 GG/del 분별위8례（12．3％）、24례（36．9％）화33례（50．8％）。AG/ins-del적Cmax 、AUC0-t 、AUC0-∞현저고우 AA/ins화GG/del ，차이유통계학의의（P＜0．05），AA/ins화GG/del지간차이무통계학의의（P＞0．05）；Tmax 、T1/2재3충기인형간차이무통계학의의（P＞0．05）。결론 rs2282143다태성여이갑쌍고약대동역학무상관성，완전련쇄적 rs628031화 rs36056065여이갑쌍고약대동역학밀절상관。
Objective To explore the effects of organic cation transporter 1(OCT1) gene rs2282143(P341L , 1022C> T) ,rs628031(M408V ,1222A> G) and rs36056065(ins/del GTAAGTTG) polymorphisms on metformin pharmacokinetics in healthy volunteers .Methods 65 healthy men were given a single oral dose of 500 mg metformin , and the plasma concentrations of metformin were measured for up to 24 h by LC-MS/MS .The subjects were divided into different groups according to polymorphisms of rs2282143 ,rs628031 and rs36056065 .Results The allele CC ,CT and TT of the rs2282143 were 45(69 .2% ) ,19(29 .2% ) and 1(1 .5% ) in 65 subjects ,respectively .There was no difference of Cmax ,Tmax ,AUC0-t ,AUC0-∞ and T1/2 between CC and CT in the rs2282143 .The polymorphisms rs628031 and rs36056065 were completely linkage disequilibrium and the presence of allele AA/ins、AG/ins-del and GG/del were 8(12 .3% ) ,24(36 .9% ) and 33(50 .8% ) in our subjects ,respectively .The Cmax ,AUC0-t ,AUC0-∞ of al-lele AG/ins-del were significantly higher than the allele AA/ins and GG/del ,whereas no difference was observed be-tween the allele AA/ins and GG/del ,respectively (P< 0 .05) .For the comparison of Tmax and T1/2 ,there were no difference among the allele AA/ins ,AG/ins-del and GG/del(P>0 .05) .Conclusion There was no effect of the poly-morphism rs2282143 on metformin pharmacokinetics .The polymorphisms rs628031 and rs36056065 that were in completely linkage disequilibrium significantly associated with metformin pharmacokinetics .