Nutescu Edith A, Shapiro Nancy L, Chevalier Aimee
Department of Pharmacy Practice, Antithrombosis Center, University of Illinois at Chicago, College of Pharmacy and Medical Center, 833 South Wood Street, M/C 886, Room 164, Chicago, IL 60612, USA.
Cardiol Clin. 2008 May;26(2):169-87, v-vi. doi: 10.1016/j.ccl.2007.12.005.
Decades of research have been devoted to developing effective, safe, and convenient anticoagulant agents. In recent years, much emphasis has been placed on the development of direct thrombin inhibitors (DTIs) that offer benefits over agents like heparin and warfarin including the inhibition of both circulating and clot-bound thrombin; a more predictable anticoagulant response, because they do not bind to plasma proteins and are not neutralized by platelet factor 4; lack of required cofactors, such as antithrombin or heparin cofactor II; inhibiting thrombin-induced platelet aggregation; and absence of induction of immune-mediated thrombocytopenia. Various injectable DTIs are currently available and used for many indications. In addition, research is now focusing on oral DTIs that seem promising and offer various advantages, such as oral administration, predictable pharmacokinetics and pharmacodynamics, a broad therapeutic window, no routine monitoring, no significant drug interactions, and fixed-dose administration.
数十年来，人们一直致力于研发有效、安全且便捷的抗凝剂。近年来，直接凝血酶抑制剂（DTIs）的研发备受关注，这类药物相较于肝素和华法林等药物具有诸多优势，包括抑制循环中的凝血酶和与血栓结合的凝血酶；抗凝反应更具可预测性，因为它们不与血浆蛋白结合，也不会被血小板因子4中和；无需抗凝血酶或肝素辅因子II等辅助因子；抑制凝血酶诱导的血小板聚集；以及不会引发免疫介导的血小板减少症。目前已有多种注射用DTIs可供使用，并用于多种适应症。此外，现在的研究重点是口服DTIs，这类药物似乎很有前景，具有多种优势，如口服给药、可预测的药代动力学和药效学、较宽的治疗窗、无需常规监测、无显著药物相互作用以及固定剂量给药。
