有机阴离子转运多肽1B1(OATP1B1)遗传多态性对瑞格列奈药动学的影响
Chinese Journal of Clinical Pharmacology and Therapeutics(2009)
Abstract
目的:研究有机阴离子转运多肽1B1(OATP1B1)遗传多态性对瑞格列奈药动学的影响.方法:16名健康男性受试者单剂量po 4 mg瑞格列奈片,并考察其SLCO1B1(OATP1B1的编码基因)常见单体型(SLCO181~*1a、~*1b、~*5和~*15),按基因型将其分成~*1b/~*1b、~*1a/~*1a或~*1a/~*1b、~*1a/~*15或~*1b/~*15三组.采用HPLC-MS-MS法测定给药后不同时间瑞格列奈的血药浓度.利用DAS2.0计算药动学参数和SPSS 12.0评价统计学差异.结果:SLCO1B1~*1b/~*1b、SLCO1B1~*1a/~*1a或~*1a/~*1b和SLCO1B1~*1a/~*15或~*1b/~*15三组受试者的AUC_(0-8h)分别为(63±20)、(70±26)和(82±24)μg·L~(-1)·h,C_(max)分别为(56±16)、(52±17)和(58±34)μg/L,三者之间差异没有统计学意义.结论:OATP1B1遗传多态性对瑞格列奈药动学有影响,但从本试验结果看,三组之间的差异较小,还不足以影响临床用药的安全性和有效性.
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Key words
genetic polymorphism,organic anion transporting polypeptide 1B1,pharmacokinetics,repaglinide
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