Department of Pharmacy, First Affiliated Hospital of Nanchang University, Nanchang, China.
Cardiovasc Ther. 2012 Oct;30(5):e234-41. doi: 10.1111/j.1755-5922.2011.00290.x. Epub 2011 May 25.
The aim of this review is to provide useful information not only for studying the effect of OATP1B1 and/or BCRP gene mutation on pharmacokinetics of novle statins of pitavastatin and rosuvastatin but also for studying drug-drug interactions (DDI) between the novle statins and other substrates of OATP1B1 and/or BCRP. Intra- and inter-ethnic differences in pharmacokinetic profiles of clinically relevant drugs are important issues reported in many papers not only for scenes of appropriate drug used in clinical settings but also for those of the drug development. Pharmacogenomics is extremely useful for understanding these racial differences. Recent pharmacogenetics study have disclosed important roles of drug transporters in the pharmacokinetic (PK) profiles of some clinically relevant drugs. In this presentation, we introduce single nucleotide polymorphisms (SNPs) of OATP1B1 and BCRP and review the contribution of genetic polymorphisms of the transporters to the pharmacokinetics of dual substrates as pitavastatin and rosuvastatin from recent study. At the same time, the DDIs between pitavastatin or rosuvastatin and other drug have been extensively concerned because of inhibiting OATP1B1-mediated hepatic uptake or BCRP-mediated hepatic efflux of pitavastatin and rosuvastatin. This review summarized the current studies about the role of OATP1B1 and BCRP in DDIs between pitavastatin or rosuvastatin and other clinically relevant drugs. The role of OATP1B1 and BCRP gene mutation can affect the PK profiles of pitavastatin and rosuvastatin. The DDIs between the novle statins and other substrates of OATP1B1 or BCRP may occur and cause change in the pharmacokinetic of the novle statins.
本综述的目的不仅在于提供有关 OATP1B1 和/或 BCRP 基因突变对新型他汀类药物匹伐他汀和瑞舒伐他汀药代动力学影响的有用信息，还在于研究新型他汀类药物与 OATP1B1 和/或 BCRP 的其他底物之间的药物相互作用（DDI）。在许多文献中，临床相关药物的药代动力学特征的种内和种间差异是重要问题，不仅涉及临床环境下适当药物的使用场景，还涉及药物开发场景。药物基因组学对于理解这些种族差异非常有用。最近的药物遗传学研究揭示了药物转运体在一些临床相关药物的药代动力学（PK）特征中的重要作用。在本演讲中，我们介绍了 OATP1B1 和 BCRP 的单核苷酸多态性（SNP），并从最近的研究中综述了转运体的遗传多态性对匹伐他汀和瑞舒伐他汀等双重底物药代动力学的贡献。同时，由于抑制匹伐他汀和瑞舒伐他汀的 OATP1B1 介导的肝摄取或 BCRP 介导的肝外排，匹伐他汀或瑞舒伐他汀与其他药物之间的 DDI 受到广泛关注。本综述总结了目前关于 OATP1B1 和 BCRP 在匹伐他汀或瑞舒伐他汀与其他临床相关药物之间 DDI 中作用的研究。OATP1B1 和 BCRP 基因突变可影响匹伐他汀和瑞舒伐他汀的 PK 特征。新型他汀类药物与 OATP1B1 或 BCRP 的其他底物之间的 DDI 可能发生，并导致新型他汀类药物的药代动力学发生变化。
