Shnayder Natalia A, Petrova Marina M, Shesternya Pavel A, Savinova Alina V, Bochanova Elena N, Zimnitskaya Olga V, Pozhilenkova Elena A, Nasyrova Regina F
The Centre of Personalized Psychiatry and Neurology, V. M. Bekhterev National Medical Research Center for Psychiatry and Neurology (V.M. Bekhterev NMRC PN) 3, Bekhterev Str., 192019 Saint-Petersburg, Russia.
The CoreFacilities Molecular and Cell Technologies, V. F. Voino-Yasenetsky Krasnoyarsk State Medical University (V.F. Voino-YasenetskyKrasSMU) 1, PartizanZheleznyak Str., 660022 Krasnoyarsk, Russia.
Biomedicines. 2021 Apr 22;9(5):451. doi: 10.3390/biomedicines9050451.
Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.
达比加群、利伐沙班、阿哌沙班和依度沙班是直接口服抗凝剂（DOACs），在全球范围内的使用日益广泛。考虑到它们在心脏病学、神经病学、骨科和2019冠状病毒病（COVID - 19）中预防血栓栓塞的广泛应用，以及它们不同的药代动力学和药物遗传学依赖性，探索DOACs给药的新机会并预测其作为单一疗法或与其他药物联合使用时的剂量至关重要。在这篇综述中，我们描述了DOACs药代动力学相关药物遗传学的细节，以及有关决定所需剂量和药物不良反应（ADR）风险的临床特征的新数据。还讨论了在开始使用DOACs之前和之后不久基因信息的有用性。特别关注这些问题的原因不仅在于新的基因知识和基因分型可能性，还在于严重ADR（主要是胃肠道出血）的风险。考虑到编码生物转化酶和DOACs代谢的基因的单核苷酸变异（SNV）携带者的影响，对于接受抗凝治疗的血栓栓塞高风险患者，采用这些措施对于预测药代动力学变化和ADR风险很重要。
