Biomnis, 78 Avenue de Verdun, 94208 Ivry-sur-Seine Cedex, France.
Thromb Res. 2010 Oct;126(4):e286-93. doi: 10.1016/j.thromres.2010.07.015.
Edoxaban (the free base of DU-176b) is a new, oral direct Factor Xa inhibitor. This is the first study to compare the hemostatic response to edoxaban, ximelagatran, and dalteparin in healthy, elderly adults.
In this open-label, active-controlled clinical trial, 40 adults (65-75 years), were randomised to: oral edoxaban (60 mg, twice-daily, 7 doses), subcutaneous dalteparin (5000 IU, once-daily, 4 doses), oral ximelagatran (24 mg, twice-daily, 7 doses) or no drug. Blood samples were taken before, and 1.5, 4, 12, 24, 72, 84, 96, 108, 120, and 144 hours after, the first dose. The primary outcomes were changes in thrombin-antithrombin complex, prothrombin fragment 1+2 and D-dimer, and adverse events. Additional biomarkers of coagulation, and endothelial cell and platelet activation were compared (ANOVA).
All subjects completed the study. Inhibition of thrombin generation lag time, peak, and constant velocity index were significantly greater, and extended for a longer period of time, following edoxaban administration, compared with dalteparin. We found that the traditional assay for anti-FXa activity was not appropriate for the new anticoagulants. Biomarker changes following edoxaban administration (including prolongation of prothrombin time) reflected inhibition of Factor Xa; there was no effect on platelet, tissue factor or endothelial activation. There were no clinically significant changes in primary outcomes. No serious adverse events were reported.
Oral administration of edoxaban resulted in effective Factor Xa and TG inhibition, and was well-tolerated. Studies are needed to confirm edoxaban (60 mg daily) use in clinical practice.
Daiichi Sankyo Pharma Development.
依度沙班（DU-176b 的游离碱）是一种新型的、口服的直接 Xa 因子抑制剂。这是第一项比较依度沙班、西米拉坦和达肝素在健康老年人群中的止血反应的研究。
在这项开放标签、活性对照的临床试验中，40 名成年人（65-75 岁）被随机分为：口服依度沙班（60mg，每日两次，7 剂）、皮下达肝素（5000IU，每日一次，4 剂）、口服西米拉坦（24mg，每日两次，7 剂）或不给予药物。在首次给药前和给药后 1.5、4、12、24、72、84、96、108、120 和 144 小时采集血样。主要结局是凝血酶-抗凝血酶复合物、凝血酶原片段 1+2 和 D-二聚体的变化以及不良事件。比较了凝血、内皮细胞和血小板激活的其他生物标志物（方差分析）。
所有受试者均完成了研究。与达肝素相比，依度沙班给药后凝血酶生成时间滞后、峰值和恒速指数的抑制作用更大，持续时间更长。我们发现，传统的抗 Xa 活性测定方法不适用于新型抗凝剂。依度沙班给药后的生物标志物变化（包括凝血酶原时间延长）反映了 Xa 因子的抑制作用；对血小板、组织因子或内皮细胞激活没有影响。主要结局无临床意义的变化。未报告严重不良事件。
口服依度沙班可有效抑制 Xa 因子和 TG，且耐受性良好。需要进一步研究来确认依度沙班（每日 60mg）在临床实践中的应用。
第一三共制药研发。
