Benmira Sihame, Banda Zuliana K, Bhattacharya Vish
Newcastle University Medical School, Newcastle University, Newcastle upon Tyne, UK.
Recent Pat Cardiovasc Drug Discov. 2010 Jun;5(2):120-37. doi: 10.2174/157489010791515269.
Heparin, low molecular weight heparin (LMWH) and warfarin are well-established anticoagulants still in widespread use despite their well known drawbacks. Heparin requires continuous monitoring, has serious side-effects such as haemorrhage, thrombosis and osteoporosis, and lacks an oral route of administration. LMWH is a safer, more convenient anticoagulant to use but it cannot be given orally, does not have an antidote and may be difficult to administer in patients with renal failure. Warfarin has a narrow therapeutic window, interacts with other drugs and foods and requires monitoring like heparin. The limitations of all three of these established anticoagulants have prompted the search for better more convenient agents. The major examples of these newer anticoagulants are the direct and indirect factor Xa inhibitors and the direct thrombin inhibitors. These new agents tend to have more predictable pharmacokinetic properties, superior efficacy and safety and some can be administered orally. In this review, we summarise the advantages and disadvantages of three established anticoagulants (heparin, LMWH and warfarin) and the most promising new anticoagulants (fondaparinux, idraparinux, rivaroxaban, apixaban, dabigatran and ximelagatran) by discussing their pharmacodynamics and pharmacokinetics. We also discuss recent patents in the field of anticoagulation, which aim to improve the safety and effectiveness of antithrombotic agents currently in use or offer alternative ways for anticoagulation.
肝素、低分子量肝素（LMWH）和华法林是已被广泛使用的成熟抗凝剂，尽管它们存在众所周知的缺点。肝素需要持续监测，有严重的副作用，如出血、血栓形成和骨质疏松，并且缺乏口服给药途径。低分子量肝素是一种使用起来更安全、更方便的抗凝剂，但它不能口服，没有解毒剂，并且在肾衰竭患者中可能难以给药。华法林的治疗窗较窄，会与其他药物和食物相互作用，并且像肝素一样需要监测。这三种成熟抗凝剂的局限性促使人们寻找更好、更方便的药物。这些新型抗凝剂的主要例子是直接和间接Xa因子抑制剂以及直接凝血酶抑制剂。这些新药往往具有更可预测的药代动力学特性、更高的疗效和安全性，并且有些可以口服。在本综述中，我们通过讨论三种成熟抗凝剂（肝素、低分子量肝素和华法林）以及最有前景的新型抗凝剂（磺达肝癸钠、依达肝素、利伐沙班、阿哌沙班、达比加群和希美加群）的药效学和药代动力学，总结了它们的优缺点。我们还讨论了抗凝领域的近期专利，这些专利旨在提高目前使用的抗血栓药物的安全性和有效性，或提供抗凝的替代方法。
