Bauer Kenneth A
Hematology Division, VA Boston HealthCare System and Beth Deaconess Medical Center, Boston, Massachusetts 02215, USA.
Am J Orthop (Belle Mead NJ). 2002 Nov;31(11 Suppl):4-10.
The synthetic pentasaccharide fondaparinux is the first in a novel class of antithrombotic agents. By selectively inactivating factor Xa in an antithrombin-dependent mechanism of action, fondaparinux exerts its anticoagulant effect through inhibition of thrombin generation, without any direct effect on thrombin activity. Unlike unfractionated heparin and low-molecular-weight heparins, fondaparinux is a single molecular entity produced by total chemical synthesis. Its favorable pharmacokinetic profile and pharmacodynamics allow for safe and effective once-daily dosing in the majority of populations. Initial clinical development of fondaparinux has focused on the prevention of venous thromboembolism following major orthopedic surgery--that is, hip and knee replacement and hip fracture. Results of the largest phase III clinical trial program to date in these major hip and knee surgeries demonstrate comparable safety, in terms of clinically relevant bleeding, and an overall 55% reduction in risk of venous thromboembolism with fondaparinux relative to the low-molecular-weight heparin enoxaparin.
合成五糖磺达肝癸钠是新型抗血栓药物中的首个药物。磺达肝癸钠通过抗凝血酶依赖性作用机制选择性地使Xa因子失活，通过抑制凝血酶生成发挥抗凝作用，而对凝血酶活性无任何直接影响。与普通肝素和低分子肝素不同，磺达肝癸钠是通过全化学合成产生的单一分子实体。其良好的药代动力学特征和药效学特性使得在大多数人群中每日一次给药安全有效。磺达肝癸钠的初始临床开发集中于预防大型骨科手术后的静脉血栓栓塞，即髋关节和膝关节置换术以及髋部骨折。迄今为止在这些大型髋关节和膝关节手术中开展的最大规模III期临床试验项目结果表明，在临床相关出血方面，安全性相当，并且与低分子肝素依诺肝素相比，磺达肝癸钠使静脉血栓栓塞风险总体降低55%。
