Choi J H, Lee M G, Cho J-Y, Lee J-E, Kim K H, Park K
Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
Clin Pharmacol Ther. 2008 Feb;83(2):251-7. doi: 10.1038/sj.clpt.6100267. Epub 2007 Jun 13.
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 (Cmax) 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 OATP1B115/*15 subjects than the others, suggesting a potential association between the OATP1B1 genetic polymorphisms and altered rosuvastatin pharmacokinetics in Korean populations.
本研究旨在确定有机阴离子转运多肽1B1（OATP1B1）基因多态性是否对韩国人群中瑞舒伐他汀的药代动力学产生影响。在200名对OATP1B1基因c.388A>G和c.521T>C进行基因分型的受试者中，选取30名进行瑞舒伐他汀药代动力学研究。瑞舒伐他汀在第1组（*1a/*1a、*1a/*1b、*1b/*1b）、第2组（*1a/*15、*1b/*15）和第3组（*15/*15）中从0至无穷大的浓度-时间曲线下面积（AUC(0-∞)）分别为111±49.3、126±45.2和191±31.0 ng·h/ml，三组之间存在显著差异（P=0.0429），*15/15组与其他组之间也存在显著差异（P=0.0181）。最大血浆浓度（Cmax）在15/15组与其他组之间也显示出显著差异（P=0.0181）。三组之间瑞舒伐他汀内酯的药代动力学无显著差异。OATP1B115/*15受试者中瑞舒伐他汀的药代动力学暴露高于其他受试者，这表明在韩国人群中OATP1B1基因多态性与瑞舒伐他汀药代动力学改变之间可能存在关联。
