Influence of OATP1B1 genotype on the pharmacokinetics of rosuvastatin in Koreans
Influence of OATP1B1 genotype on the pharmacokinetics of rosuvastatin in Koreans
复制标题
DOI：
10.1038/sj.clpt.6100267
复制
发表时间：
2008-02-01
影响因子：
6.7
通讯作者：
Park, K.
中科院分区：
文献类型：
--
作者：
Choi, J. H.;Lee, M. G.;Park, K.
本研究旨在确定有机阴离子转运多肽1B 1（OATP 1B 1）多态性是否对韩国人中瑞舒伐他汀的药代动力学产生影响。在200例基因分型为OATP 1B 1 c.388A>G和c.521T>C的受试者中，选择30例受试者进行瑞舒伐他汀药代动力学研究。0至无穷大的浓度-时间曲线下面积第1组瑞舒伐他汀的AUC（0-无穷大）（*1a/*1a，*1a/*1b，*1b/*1b），第2组（*1a/*15，*1b/*15）和第3组（*15/*15）分别为111 +/- 49.3，126 +/- 45.2和191 +/- 31.0 ng h/ml，三组间差异有统计学意义（P=0.0429），（*15/*15）与其他组间差异有统计学意义（P=0.0181）。最大血药浓度（C-max）也显示（*15/*15）与其他组之间存在显著差异（P=0.0181）。三组间瑞舒伐他汀-内酯药代动力学无显著差异。OATP 1B 1 *15/*15受试者中瑞舒伐他汀的药代动力学暴露量高于其他受试者，表明韩国人群中OATP 1B 1基因多态性与瑞舒伐他汀药代动力学改变之间存在潜在相关性。
This study was carried out to determine whether polymorphisms of organic anion-transporting polypeptide 1B1 (OATP1B1) have an effect on rosuvastatin pharmacokinetics in Koreans. Among 200 subjects genotyped for OATP1B1 c.388A>G, and c.521T>C, 30 subjects were selected for the rosuvastatin pharmacokinetic study. The area under the concentration-time curve for 0 to infinity (AUC(0-infinity)) of rosuvastatin for group 1 (*1a/*1a, *1a/*1b, *1b/*1b), group 2 (*1a/*15, *1b/*15), and group 3 (*15/*15) were 111 +/- 49.3, 126 +/- 45.2, and 191 +/- 31.0 ng h/ml, respectively, with significant differences among the three groups (P=0.0429) and between (*15/*15) and the other groups (P=0.0181). The maximum plasma concentration (C-max) also showed a significant difference between (*15/*15) and the other groups (P=0.0181). There were no significant differences in rosuvastatin-lactone pharmacokinetics among the three groups. The pharmacokinetic exposure of rosuvastatin was higher in the OATP1B1*15/*15 subjects than the others, suggesting a potential association between the OATP1B1 genetic polymorphisms and altered rosuvastatin pharmacokinetics in Korean populations.