Is ethnic variability in the exposure to rosuvastatin explained only by genetic polymorphisms in OATP1B1 and BCRP or should the contribution of intrinsic ethnic differences in OATP1B1 be considered?
Is ethnic variability in the exposure to rosuvastatin explained only by genetic polymorphisms in OATP1B1 and BCRP or should the contribution of intrinsic ethnic differences in OATP1B1 be considered?
复制标题
瑞舒伐他汀暴露的种族差异是否只能通过 OATP1B1 和 BCRP 的遗传多态性来解释，还是应该考虑 OATP1B1 的内在种族差异？
DOI：
10.1016/j.xphs.2017.04.074
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Toshimoto K.
中科院分区：
文献类型：
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作者：
Sugiyama Y;Maeda K;Toshimoto K.
众所周知，亚洲受试者的瑞舒伐他汀暴露量比白人对照高出约 2 倍。 1, 2 我的研究小组在 2013 年发表了一份报告，表明他汀类药物血浆暴露的种族变异性不能完全用有机阴离子转运多肽（OATP）1B1 和乳腺癌抗性蛋白（BCRP）等位基因频率的差异来解释，并建议必须考虑 OATP1B1 活性的内在种族变异性（日本人和白种人之间的活性比率为 0.584）。 3 这项基于扩展清除概念的分析是利用许多已发表的关于他汀类药物（包括瑞舒伐他汀）药代动力学种族差异的临床观察结果进行的。 3 在本期《药物科学杂志》特刊中，Wu 等人。 4 发表了一篇题为“在控制和抑制条件下，亚洲和白人野生型 OATP1B1 和 BCRP 的瑞舒伐他汀药代动力学”的论文，得出的结论是，OATP1B1 和 BCRP 的多态性比单独的种族更能预测瑞舒伐他汀暴露。这一结论是从他们的临床研究中得出的，这是一项在健康白人和亚洲志愿者中进行的双组、随机、交叉瑞舒伐他汀药代动力学研究，该研究表明，当所有受试者都是两种转运蛋白野生型等位基因的携带者时，亚洲人和白人的瑞舒伐他汀暴露量没有显着差异。因此，我们的研究 3 和 Wu 等人的研究。 4人似乎得出了不同的结论。我们如何解释这些明显的差异？本评论的目的是对这些差异提出一些可能的解释。
It is widely known that there is an approximately 2-fold higher exposure to rosuvastatin in Asian subjects compared with Caucasian controls. 1, 2 My group published a report in 2013 indicating that the ethnic variability in the plasma exposure to statins cannot be fully explained by the difference in the allele frequencies of organic anion transporting polypeptide (OATP) 1B1 and breast cancer resistance protein (BCRP), and suggesting that the intrinsic ethnic variability in the activity of OATP1B1 (the ratio of activity between Japanese and Caucasians is 0.584) must be considered. 3 This analysis based on the extended clearance concept was performed using many published clinical observations on ethnic variability in the pharmacokinetics of statins including rosuvastatin. 3 In this special issue of the Journal of Pharmaceutical Sciences, Wu et al. 4 published a paper entitled “Rosuvastatin pharmacokinetics in Asian and White subjects wild type for both OATP1B1 and BCRP under control and inhibited conditions” which concluded that polymorphisms in both OATP1B1 and BCRP are better predictors of rosuvastatin exposure than ethnicity alone. This conclusion was drawn from their clinical study, a 2-arm, randomized, cross-over rosuvastatin pharmacokinetics study in healthy White and Asian volunteers, which showed that rosuvastatin exposure in Asians and Whites did not differ significantly when all subjects were carriers of the wild-type alleles of both transporters. Therefore, our study 3 and that by Wu et al. 4 appear to have reached different conclusions. How can we interpret these apparent differences? The purpose of this commentary is to propose some possible explanations for the differences.