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Ximelagatran(Xim)系凝血酶抑制药,一种新型的口服抗凝药物,对脑卒中、急性冠脉综合征、矫形外科术后深静脉血栓栓塞和静脉血栓栓塞的防治,取得较好的疗效。Xim致大出血的危险性较少见,不需频繁的血凝监测,可作为华发林的替代药物,是抗凝药物领域中的重大突破。本文综合介绍Xim的药理作用、临床应用和不良反应。1 药理作用Xim是一种合成的直接凝血酶抑制药,分子量429。Ximelagatran经分解为美拉加群(melagatran,Mel)发挥抗凝血作用。Mel可迅速、可逆性和竞争性与凝血酶结合,以阻止纤维蛋白原转变为纤维蛋白,有效地阻断终末凝血阶段的进程。但是,Mel口服吸收不良,从而研制出Mel前体药物Xim。Xim口服后能迅速吸收并水解为Mel。口服Xim后血浆峰Mel浓度为2 h。一经转换为Mel,约80%从尿液排泄, 其余部分通过胆汁排泄。Mel与血浆蛋白质结合较低(< 15%),分布容积小(0.22/kg)。在健康志愿者中,终末排泄半衰期为1.7-2.0 h。Xim的吸收和转变为Mel的速度与年龄无关,食物不影响本药的吸收。对细胞色素P450酶系如CYP2C9、CYP2C19和CYP3A4无明显抑制和诱导作用,故与经这些酶代谢的药物没有相互作用。
Ximelagatran (Xim), a thrombin inhibitor, is a new oral anticoagulant that has been shown to be effective in the prevention and treatment of stroke, acute coronary syndrome, orthopedic postoperative deep vein thrombosis and venous thromboembolism. The risk of major bleeding due to Xim is less common, and frequent monitoring of blood coagulation is not required. As an alternative medicine to Huafaarin, Xim is a major breakthrough in the field of anticoagulant drugs. This article describes the pharmacological effects of Xim, clinical applications and adverse reactions. 1 pharmacological effects Xim is a synthetic direct thrombin inhibitor, molecular weight 429. Ximelagatran decomposes into melagatran (Mel) to exert anticoagulant effects. Mel rapidly, reversibly and competitively binds thrombin to prevent the conversion of fibrinogen to fibrin, effectively blocking the progression of the terminal clotting phase. However, Mel oral malabsorption, resulting in the development of Mel prodrug Xim. Xim quickly absorbed and hydrolyzed to Mel after oral administration. Peak plasma Mel concentration after oral administration of Xim was 2 h. Once converted to Mel, about 80% excreted from the urine, the rest excreted through the bile. Mel and plasma protein binding is low (<15%), the distribution of small volume (0.22 / kg). In healthy volunteers, the terminal excretion half-life of 1.7-2.0 h. The rate at which Xim absorbs and changes to Mel has nothing to do with age, and the food does not affect the absorption of the drug. Cytochrome P450 enzymes such as CYP2C9, CYP2C19 and CYP3A4 no significant inhibitory and inductive effect, so the enzyme metabolism of these enzymes have no interaction.