McBride Brian F
Electrophysiologic and Metabolic Pharmacogenomics, Division of Clinical Pharmacology, Vanderbilt University School of Medicine, 536 Robinson Research Building, Nashville, TN 37232, USA.
J Clin Pharmacol. 2005 Sep;45(9):1004-17. doi: 10.1177/0091270005278084.
Chronic anticoagulation represents a clinical conundrum for the health care community that balances unquestionable morbidity and mortality benefits against interindividual variability, leading to drug interactions, adverse events, and thromoembolic events related to underdosing. Despite the growing data regarding the appropriate use and dosing of agents used for chronic anticoagulation, use in clinical practice remains low, thus leading to a theoretical reduction in the risk-to-benefit ratio in the clinical setting relative to that reported in the literature. Oral anticoagulants currently in development represent a heterogeneous group of compounds that are specific for the final common pathway in the coagulation cascade and show indications toward a reduced drug interaction profile, reduced interpatient variation in pharmacokinetic parameters, and morbidity and mortality benefits that might be similar to currently available treatment modalities. This review highlights the critical differences among oral anticoagulants in development and places their role in the context of the benefits and limitations of currently available anticoagulants.
长期抗凝治疗对医疗界来说是一个临床难题，需要在明确的发病率和死亡率获益与个体差异之间进行权衡，而个体差异会导致药物相互作用、不良事件以及因剂量不足引起的血栓栓塞事件。尽管关于慢性抗凝治疗药物的合理使用和剂量的资料越来越多，但在临床实践中的应用率仍然很低，因此与文献报道相比，临床环境中理论上的风险效益比有所降低。目前正在研发的口服抗凝剂是一组异质性化合物，它们作用于凝血级联反应的最终共同途径，显示出药物相互作用减少、药代动力学参数的患者间差异减小以及发病率和死亡率获益可能与现有治疗方式相似的迹象。这篇综述强调了正在研发的口服抗凝剂之间的关键差异，并在现有抗凝剂的获益和局限性背景下阐述了它们的作用。
