The direct thrombin inhibitor dabigatran etexilate is currently in phase III of development for the prophylaxis and treatment of thromboembolic disorders, with three trials completed in primary venous thromboembolism (VTE) prevention. Dabigatran etexilate is an orally administered prodrug, which is rapidly absorbed and converted to the active form, dabigatran. Dabigatran has been shown to specifically and reversibly inhibit thrombin, the key enzyme in the coagulation cascade. Studies in healthy volunteers and in patients undergoing orthopaedic surgery have indicated that dabigatran has a predictable pharmacokinetic/pharmacodynamic profile, allowing for a fixed-dose regimen. Peak plasma concentrations of dabigatran are reached approximately 2 hours after oral administration in healthy volunteers, with no unexpected accumulation of drug concentrations upon multiple dosing. Excretion is predominantly via the renal route as unchanged drug. Dabigatran is not metabolized by cytochrome P450 isoenzymes. The small differences in dabigatran pharmacokinetics associated with age and gender are attributed to variations in renal function. Additional studies have shown that the pharmacokinetic/pharmacodynamic profile of dabigatran is consistent across a range of patient populations, with no effect of moderate hepatic impairment being observed. Drug-drug interactions are not observed with concomitant administration of atorvastatin, diclofenac or digoxin. The pharmacodynamic profile of dabigatran demonstrates effective anticoagulation combined with a low risk of bleeding. Further phase III studies are ongoing, including acute VTE treatment and stroke prevention in atrial fibrillation; the results obtained so far show that dabigatran etexilate is well tolerated and effective in the treatment and prevention of thromboembolic events.

译文

直接凝血酶抑制剂达比加群酯目前处于预防和治疗血栓栓塞性疾病的III期开发阶段,完成了预防原发性静脉血栓栓塞 (VTE) 的三项试验。达比加群酯是一种口服前药,可迅速吸收并转化为活性形式达比加群。达比加群已被证明可以特异性和可逆地抑制凝血酶,凝血酶是凝血级联反应中的关键酶。在健康志愿者和接受骨科手术的患者中进行的研究表明,达比加群具有可预测的药代动力学/药效学特征,可以采用固定剂量的方案。在健康志愿者中,口服给药后约2小时达到达比加群的血浆峰值浓度,多次给药后没有意外的药物浓度积累。排泄主要通过肾脏途径作为未改变的药物。达比加群不被细胞色素P450同工酶代谢。与年龄和性别相关的达比加群药代动力学的微小差异归因于肾功能的变化。其他研究表明,达比加群的药代动力学/药效学特征在一系列患者人群中是一致的,没有观察到中度肝损害的影响。阿托伐他汀,双氯芬酸或地高辛的同时给药未观察到药物相互作用。达比加群的药效学特征表明,抗凝有效,出血风险低。进一步的III期研究正在进行中,包括房颤的急性VTE治疗和中风预防; 到目前为止获得的结果表明,达比加群酯具有良好的耐受性,并且在治疗和预防血栓栓塞事件方面有效。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录