Bayer Pharma AG, Clinical Pharmacology, D-42096 Wuppertal, Germany.
Thromb J. 2013 Jun 28;11(1):10. doi: 10.1186/1477-9560-11-10.
Unlike traditional anticoagulants, the more recently developed agents rivaroxaban, dabigatran and apixaban target specific factors in the coagulation cascade to attenuate thrombosis. Rivaroxaban and apixaban directly inhibit Factor Xa, whereas dabigatran directly inhibits thrombin. All three drugs exhibit predictable pharmacokinetic and pharmacodynamic characteristics that allow for fixed oral doses in a variety of settings. The population pharmacokinetics of rivaroxaban, and also dabigatran, have been evaluated in a series of models using patient data from phase II and III clinical studies. These models point towards a consistent pharmacokinetic and pharmacodynamic profile, even when extreme demographic factors are taken into account, meaning that doses rarely need to be adjusted. The exception is in certain patients with renal impairment, for whom pharmacokinetic modelling provided the rationale for reduced doses as part of some regimens. Although not routinely required, the ability to measure plasma concentrations of these agents could be advantageous in emergency situations, such as overdose. Specific pharmacokinetic and pharmacodynamic characteristics must be taken into account when selecting an appropriate assay for monitoring. The anti-Factor Xa chromogenic assays now available are likely to provide the most appropriate means of determining plasma concentrations of rivaroxaban and apixaban, and specific assays for dabigatran are in development.
与传统抗凝剂不同，最近开发的药物利伐沙班、达比加群和阿哌沙班针对凝血级联中的特定因素，以减弱血栓形成。利伐沙班和阿哌沙班直接抑制因子 Xa，而达比加群直接抑制凝血酶。所有这三种药物都表现出可预测的药代动力学和药效学特征，可在多种情况下使用固定的口服剂量。利伐沙班和达比加群的群体药代动力学已在一系列模型中进行了评估，这些模型使用来自 II 期和 III 期临床试验的患者数据。这些模型表明，即使考虑到极端的人口统计学因素，也存在一致的药代动力学和药效学特征，这意味着很少需要调整剂量。例外情况是在某些肾功能受损的患者中，对于这些患者，药代动力学模型为某些方案中的剂量减少提供了依据。尽管通常不需要，但在紧急情况下（如过量），测量这些药物的血浆浓度的能力可能是有利的。在选择合适的监测检测方法时，必须考虑特定的药代动力学和药效学特征。目前可用的抗因子 Xa 显色检测法可能是确定利伐沙班和阿哌沙班血浆浓度的最合适方法，并且正在开发针对达比加群的特定检测法。
