柳叶刀：在健康志愿者中达比加群酯逆转剂效果显著

-在健康人群中，特异性逆转剂idarucizumab[1] 可以迅速、完全、持久地逆转泰毕全® 的抗凝效应。

-通过五分钟单次idarucizumab输注即刻达到完全逆转，且耐受良好。

-Idarucizumab已提交美国食品药品监督管理局（FDA）、欧洲药品管理局（EMA）和加拿大卫生部进行上市审批。

2015年6月17日柳叶刀发表了特异性逆转剂idarucizumab逆转达比加群酯抗凝效应的研究结果。研究结果显示，idarucizumab可迅速、完全、持久地逆转泰毕全®的抗凝效应。研究数据表明，针对需要逆转抗凝效应的情况，例如需紧急干预治疗时，特异性拮抗剂可以提供一种具有高度靶向作用的治疗选择。1美国FDA2认定Idarucizumab为突破性治疗药物。目前，勃林格殷格翰公司已将Idarucizumab提交至FDA、EMA和加拿大卫生部进行上市审批。 3

在柳叶刀现已发表的健康志愿者研究中，参与者首先接受泰毕全®治疗，然后接受idarucizumab治疗。该实验在泰毕全®末次给药后2小时给予特异性逆转剂，此时达比加群酯的浓度处于峰值。输注idarucizumab五分钟后，抗凝作用即刻逆转至基线水平。2g或以上剂量可使逆转效应持续超过24小时。在研究参与者中，Idarucizumab耐受良好。1

“柳叶刀发表的数据表明，在健康志愿者中，idarucizumab对达比加群酯的逆转效果惊人，” 勃林格殷格翰心血管治疗领域医学副总裁Jörg Kreuzer教授表示，“一旦获批，意味着特异性新型口服抗凝药逆转剂的诞生，对于抗凝治疗具有里程碑式的意义。”

在2014年12月的美国血液学会年会上，曾公布idarucizumab在老年志愿者及肾损害志愿者人群中表现出的相似结果。4勃林格殷格翰正在开展idarucizumab在患者人群研究——RE-VERSE ADTM研究。5

更多信息

1.     Glund S, et al. Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy make volunteers: a randomised, placebo-controlled, double-blind phase 1 trial. The Lancet. Published online June 16, 2015. Available at http://dx.doi.org/10.1016/S0140-6736(15)60732-2

2.     Boehringer Ingelheim Press Release – 30 June 2014. U.S. FDA grants Breakthrough Therapy Designation to Pradaxa® (dabigatran etexilate) specific investigational antidote. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2014/30_june_2014_dabigatranetexilate.html   Last accessed April 2015.

3.     Boehringer Ingelheim Press Release – 3 March 2015. Boehringer Ingelheim submits applications for approval of idarucizumab, specific reversal agent to dabigatran etexilate (Pradaxa®), to EMA, FDA and Health Canada. http://www.boehringer-ingelheim.com/news/news_releases/press_releases/2015/03_march_2015_dabigatranetexilate.html   Last accessed April 2015.

4.     Glund S. et al. Idarucizumab, a Specific Antidote for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran Induced Anticoagulation in Elderly and Renally Impaired Subjects. Presented on 8th December at the 56th American Society of Hematology Annual Meeting & Exposition, San Francisco, USA. Available at: https://ash.confex.com/ash/2014/webprogram/Paper74960.html Last accessed April 2015.

5.     Pollack C, et al. A Phase III Clinical Trial to Evaluate the Reversal Effects of Idarucizumab on Active Dabigatran (RE-VERSE AD™). Poster presentation at the International Stroke Conference, Nashville, TN, USA, 11-13 February 2015.

6.     Boehringer Ingelheim Data on File.

7.     Pradaxa® European Summary of Product Characteristics, 2014.

8.     PRADAXAâ US Prescribing Information, 2014.

9.     Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clin Pharmacokinet. 2008;47(5):285–95.

10.   Di Nisio M. et al. Direct thrombin inhibitors. N Engl J Med. 2005;353:1028–40.

11.   Stangier J. et al. Pharmacokinetic Profile of the Oral Direct Thrombin Inhibitor Dabigatran Etexilate in Healthy Volunteers and Patients Undergoing Total Hip Replacement. J Clin Pharmacol. 2005;45:555–63.