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

摘要/Abstract

摘要： 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(SLCO1B1^*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-MSMS法测定给药后不同时间瑞格列奈的血药浓度。利用DAS 2.0 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_{0-8 h} 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。

关键词: 瑞格列奈, 有机阴离子转运多肽1B1, 遗传多态性, 药动学

Abstract: AIM: To investigate the effects of the genetic polymorphism of organic anion transporting polypeptide 1B1 (OATP1B1) on the pharmacokinetic profile of repaginide in Chinese subjects. METHODS: The common haplotypes of SLCO1B1 (the coding gene of OATP1B1), which were reported as SLCO1B1 ^* 1a, ^* 1b, ^* 5 and ^* 15, were determined in 16 healthy male volunteers with the genotypes of ^* 1b/^* 1b, ^* 1a/^* 1a or ^* 1a/^* 1b, ^* 1a/^* 15 or ^* 1b/^* 15.A single dose (4 mg) of repaglinide tablets was given orally. The plasma concentrations of repaglinide were determined by HPLC-MS-MS method. The pharmacokinetic parameters were obtained by DAS Ver 2.0.The statistical differences of the pharmacokinetic parameters were assessed by SPSS 12.0.RESULTS: The values of AUC_{0-8 h} of SLCO1B1 ^* 1b/^* 1b, SLCO1B1 ^* 1a/^* 1a or ^* 1a/^* 1b and SLCO1B1 ^* 1a/^* 15 or ^* 1b/^* 15 three groups were (63±20), (70±26) and (82±24) μg·L^-1 ·h respectively. The values of C_max were (56± 16), (52±17) and (58±34) μg/L respectively. There were no significant differences between any two groups. CONCLUSION: The pharmacokinetic profile of repaglinide was affected by the genetic polymorphism of OATP1B1, but the difference from this experiment is not large enough to affect clinical drug safety and effectiveness.

Key words: repaglinide, organic anion transporting polypeptide 1B1, genetic polymorphism, pharmacokinetics

中图分类号:

R969

阳国平, 宋敏, 谭鸿毅, 刘纯, 黄志军, 刘畅, 阳丽, 向红, 付志敏, 黄原原. 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[J]. 中国临床药理学与治疗学, 2009, 14(9): 990-994.

YANG Guo-ping, SONG Min, TAN Hong-yi, LIU Chun, HUANG Zhi-jun, LIU Chang, YANG Li, XIANG Hong, FU Zhi-min, HUANG Yuan-yuan. Effects of genetic polymorphism of OATP1B1 on pharmacokinetics of repaglinide[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(9): 990-994.

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