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新型口服抗凝药的药物遗传学:已鉴定基因变异及未来展望综述

Pharmacogenetics of novel oral anticoagulants: a review of identified gene variants & future perspectives.

作者信息

Ašić Adna, Marjanović Damir, Mirat Jure, Primorac Dragan

机构信息

Department of Genetics & Bioengineering, International Burch University, Francuske revolucije bb, 71210 Ilidža, Sarajevo, Bosnia & Herzegovina.

Institute for Anthropological Research, University of Zagreb, Ljudevita Gaja 32, 10000 Zagreb, Croatia.

出版信息

Per Med. 2018 May 1;15(3):209-221. doi: 10.2217/pme-2017-0092. Epub 2018 May 16.

Abstract

Novel oral anticoagulants (NOACs) are becoming a therapy of choice in everyday clinical practice after almost 50 years during which warfarin and related coumarin derivatives were used as the main anticoagulants. Advantages of NOACs over standard anticoagulants include their predictable pharmacodynamics and pharmacokinetics, stable plasma concentrations and less drug-drug and food-drug interactions. However, pharmacogenetics has its place in administration of NOACs, as considerable interindividual variations have been detected. In this review, previous findings in pharmacogenetics of dabigatran, rivaroxaban, apixaban and edoxaban are summarized, along with recommendations for studying genes encoding metabolically important enzymes for four selected NOACs. Future directions include identification of clinically relevant SNPs, and change in optimum dosage for patients who are carriers of significant variants.

摘要

在使用华法林及相关香豆素衍生物作为主要抗凝剂近50年后,新型口服抗凝剂(NOACs)正成为日常临床实践中的首选治疗方法。与标准抗凝剂相比,NOACs的优势包括其可预测的药效学和药代动力学、稳定的血浆浓度以及较少的药物-药物和食物-药物相互作用。然而,由于已检测到个体间存在相当大的差异,药物遗传学在NOACs的给药中也有其作用。在本综述中,总结了达比加群、利伐沙班、阿哌沙班和依度沙班药物遗传学的先前研究结果,以及针对四种选定NOACs研究编码代谢重要酶的基因的建议。未来的方向包括识别临床相关的单核苷酸多态性(SNP),以及为携带显著变异的患者改变最佳剂量。

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