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基因多态性对利伐沙班药代动力学及临床结局的影响:最新综述

Effect of Gene Polymorphism on the Pharmacokinetics and Clinical Outcomes of Rivaroxaban: State-of-the-Art Review.

作者信息

Wang Ling, Chen Guoquan, Hu Wei, Chen Jiale, He Yiling

机构信息

School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.

Department of Pharmacy, Affiliated Jinhua Hospital, Medical College of Zhejiang University, Jinhua, People's Republic of China.

出版信息

Drug Des Devel Ther. 2025 Aug 25;19:7321-7331. doi: 10.2147/DDDT.S534569. eCollection 2025.

Abstract

Rivaroxaban is a direct oral anticoagulant (DOAC) that directly inhibits coagulation factor Xa and exerts its anticoagulant effects. Although rivaroxaban generally exhibits predictable pharmacokinetic (PK) and pharmacodynamic (PD) profiles, significant interindividual variability in therapeutic responses exists. Research on the role of genetic factors in the clinical variability of rivaroxaban is relatively new and extensive. In this review, 12 pharmacogenetic studies on rivaroxaban were summarised, and 25 reported gene polymorphic sites were summarised, including (rs1045642, rs4148738, rs1128503, rs2032582, rs4728709, rs3789243 and rs3213619, (rs2231142, rs2231137, rs3114018, rs2622604 and rs1481012), (rs35599367, rs2242480, rs4646437 and rs12333983), (rs776746, rs15524, rs4646450), (rs890293), (rs4244285 and rs12248560), (rs7212506), (rs1738023 and rs1738025). The review provided an overview of the current state of research on rivaroxaban gene polymorphisms. However, due to the significant heterogeneity of existing studies and the lack of consistency in results, the evidence to date has limited impact. Therefore, larger-scale, global, multi-centre clinical trials are needed in the future to validate potential gene loci for testing.

摘要

利伐沙班是一种直接口服抗凝剂(DOAC),可直接抑制凝血因子Xa并发挥其抗凝作用。尽管利伐沙班通常表现出可预测的药代动力学(PK)和药效学(PD)特征,但治疗反应仍存在显著的个体间差异。关于遗传因素在利伐沙班临床变异性中作用的研究相对较新且广泛。在本综述中,总结了12项关于利伐沙班的药物遗传学研究,并总结了25个报道的基因多态性位点,包括(rs1045642、rs4148738、rs1128503、rs2032582、rs4728709、rs3789243和rs3213619),(rs2231142、rs2231137、rs3114018、rs2622604和rs1481012),(rs35599367、rs2242480、rs4646437和rs12333983),(rs776746、rs15524、rs4646450),(rs890293),(rs4244285和rs12248560),(rs7212506),(rs1738023和rs1738025)。该综述概述了利伐沙班基因多态性的当前研究状况。然而,由于现有研究的显著异质性和结果缺乏一致性,迄今为止的证据影响有限。因此,未来需要进行更大规模、全球性、多中心的临床试验,以验证潜在的基因位点用于检测。

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