直接口服抗凝剂的药物遗传学

N. Shnayder, M. Petrova, E. Bochanova, O. V. Zimnitskaya, A. Savinova, E. Pozhilenkova, R. Nasyrova
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引用次数: 1

摘要

50多年来,口服维生素K拮抗剂是长期治疗和预防动脉和静脉血栓栓塞事件的首选抗凝剂。近年来,四种直接口服抗凝剂(DOACs)达比加群、利伐沙班、阿哌沙班和依多沙班与华法林在预防血栓栓塞方面进行了比较。这些抗凝剂直接抑制凝血级联中的特定蛋白质;相反,口服维生素K拮抗剂抑制维生素K依赖性凝血因子的合成。达比加群是一种直接凝血酶抑制剂,利伐沙班、阿哌沙班和依多沙班是Xa因子抑制剂,它们产生更可预测、更不稳定的抗凝作用。doac没有固有的维生素K拮抗剂的限制。doac具有可预测的药代动力学特征,并且没有维生素K拮抗剂固有的药物反应。然而,有必要考虑到个体的药理学特征,这可能会影响doac使用的有效性和安全性。从目前DOACs的基础研究和临床研究的结果来看,基因组变化对DOACs的药代动力学和药效学的影响是不可否认的。然而,这些研究需要继续下去。有必要在不同的种族群体中计划和开展更大规模的研究,包括对每个记录的群体中具有明确表型的治疗方法的患者数量进行足够的关联遗传研究。
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Pharmacogenetics of Direct Oral Anticoagulants
For more than 50 years, oral vitamin K antagonists were the choice of anticoagulant for the long-term treatment and prevention of arterial and venous thromboembolic events. In recent years, four direct oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban and edoxaban have been compared with warfarin for thromboembolism prevention. These anticoagulants directly inhibit specific proteins within the coagulation cascade; in contrast, oral vitamin K antagonists inhibit the synthesis of vitamin K-dependent clotting factors. Dabigatran, a direct thrombin inhibitor, and rivaroxaban, apixaban and edoxaban, the factor Xa inhibitors, produce a more predictable, less labile anticoagulant effect. DOACs do not have limitations inherent vitamin K antagonists. DOACs have a predictable pharmacokinetic profile and are free of advers drugs reactions inherent in vitamin K antagonists. However, it is necessary to take into account the pharmacogenetic characteristics of the individual that can affect effectiveness and safety of use of DOACs. The results carried out to the present fundamental and clinical studies of DOACs studies demonstrate an undeniable the influence of genome changes on the pharmacokinetics and pharmacodynamics of DOACs. However, the studies need to be continued. There is a need to plan and conduct larger studies in various ethnic groups with the inclusion of sufficient associative genetic studies of the number of patients in each of the documented groups treatments with well-defined phenotypes.
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