生物活性

• 描述Thrombin is produced by the proteolytic cleavage of prothrombin and serves as a multifunctional serine protease with a central role in blood coagulation, platelet activation and wound healing. In pathological conditions, thrombus formation eventually leads to vascular occlusion which, inturn, can result in the development of thromboembolic disease. Dabigatran etexilate is an orally active prodrug of dabigatran which is a reversible and selective, direct thrombin inhibitor undergoing advanced clinical development. Dabigatran selectively and reversibly inhibited human thrombin (K_i: 4.5 nM) as well as thrombin-induced platelet aggregation (IC₅₀: 10 nM). Dabigatran demonstrated concentration-dependent anticoagulant effects in various species in vitro, doubling the activated partial thromboplastin time (aPTT), prothrombin time (PT) and ecarin clotting time (ECT) in human PPP (platelet-poor plasma) at concentrations of 0.23, 0.83 and 0.18 μM, respectively. In vivo, dabigatran prolonged the aPTT dose-dependently after intravenous administration in rats (0.3, 1 and 3 mg/kg) and rhesus monkeys (0.15, 0.3 and 0.6 mg/kg). Dose- and time-dependent anticoagulant effects were observed with dabigatran etexilate administered orally to conscious rats (10, 20 and 50 mg/kg) or rhesus monkeys (1, 2.5 or 5 mg/kg), with maximum effects observed between 30 and 120 min after administration, respectively^[3]. In a modified Wessler model, bolus administration of dabigatran (0.01 - 0.1 mg/kg) reduced thrombus formation dose-dependently, with an ED₅₀ of 0.033 mg/kg and complete inhibition at 0.1 mg/kg^[4].
• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02170922	Healthy	Phase 1	Completed	-	-
  NCT02666157	Atrial Fibrillation	Phase 4	Unknown	December 2018	Taiwan ... more >> National Cheng Kung University Hospital Recruiting Tainan, Tainan City, Taiwan, 704 Contact: Ting-Hsing Chao, MD    886-6-2353535 ext 2382    chaoth@mail.ncku.edu.tw    Principal Investigator: Ting-Hsing Chao, MD          Sub-Investigator: Ju-Yi Chen, MD and PhD          Sub-Investigator: Cheng-Han Lee, MD and PhD          Sub-Investigator: Chih-Chan Lin, MD          Sub-Investigator: Chih-Hung Chen, MD          Sub-Investigator: Liang-Miin Tsai, MD          Sub-Investigator: Li-Jen Lin, MD          Sub-Investigator: Wei-Chuan Tsai, MD          Sub-Investigator: Ping-Yen Liu, MD and PhD          Tainan Hospital Ministry of Health and Welfare Not yet recruiting Tainan, Tainan City, Taiwan, 704 Contact: Li-Dan Yang, MD    886-6-2200055 ext 9    litannyang@yahoo.com.tw    Principal Investigator: Li-Dan Yang, MD          National Cheng Kung University Hospital Dou-Liou Branch Not yet recruiting Dou-Liou City, Taiwan, 640 Contact: Yang-Cheh Hsueh, MD    886-5-5332121 ext 5101    p308378@dou6.hosp.ncku.edu.tw    Principal Investigator: Yang-Cheh Hsueh, MD          Sub-Investigator: Yuen-Ting Sung, MD and PhD          E-DA Hospital Not yet recruiting Kaohsiung, Taiwan, 824 Contact: Wei-Kung Tseng, MD and PhD    886-7-6150011 ext 5005    arthurtseng@me.com    Principal Investigator: Wei-Kung Tseng, MD and PhD          Tainan Municipal Hospital Recruiting Tainan, Taiwan, 701 Contact: I-Chih Chen, MD    886-6-2609926 ext 212045    ichih1230@yahoo.com.tw    Principal Investigator: I-Chih Chen, MD          Sub-Investigator: Ruei-Chang Zeng, MD Collapse <<
  NCT01468155	Atrial Fibrillation	Phase 4	Completed	-	Canada, Ontario ... more >> London Health Sciences Center London, Ontario, Canada, N6A 5A5 Collapse <<

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• 参考文献

• [1] McKellar SH, Abel S, et al. Effectiveness of dabigatran etexilate for thromboprophylaxis of mechanical heart valves. J Thorac Cardiovasc Surg. 2011 Jun;141(6):1410-6.

  [2] Wienen W, Stassen JM, et al. In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Thromb Haemost. 2007 Jul;98(1):155-62.

  [3] Wienen W, Stassen JM, Priepke H, Ries UJ, Hauel N. In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Thromb Haemost. 2007;98(1):155-162.

  [4] Wienen W, Stassen JM, Priepke H, Ries UJ, Hauel N. Effects of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate, on thrombus formation and bleeding time in rats. Thromb Haemost. 2007;98(2):333-338.