Byon W, Sweeney K, Frost C, Boyd R A
Pfizer, Groton, Connecticut, USA.
Bristol-Myers Squibb, Princeton, New Jersey, USA.
CPT Pharmacometrics Syst Pharmacol. 2017 May;6(5):340-349. doi: 10.1002/psp4.12184.
Apixaban is approved for treatment of venous thromboembolism (VTE) and prevention of recurrence. Population pharmacokinetics, pharmacokinetics-pharmacodynamics (anti-FXa activity), and exposure-response (binary bleeding and thromboembolic endpoints) of apixaban in VTE treatment subjects were characterized using data from phase I-III studies. Apixaban pharmacokinetics were adequately characterized by a two-compartment model with first-order absorption and elimination. Age, sex, and Asian race had less than 25% impact on exposure, while subjects with severe renal impairment were predicted to have 56% higher exposure than the reference subject (60-year-old non-Asian male weighing 85 kg with creatinine clearance of 100 mL/min). The relationship between apixaban concentration and anti-FXa activity was described by a linear model with a slope estimate of 0.0159 IU/ng. The number of subjects with either a bleeding or thromboembolic event was small, and no statistically significant relationship between apixaban exposure and clinical endpoints could be discerned with a logistic regression analysis.
阿哌沙班已被批准用于治疗静脉血栓栓塞症（VTE）并预防复发。利用I - III期研究的数据，对阿哌沙班在VTE治疗受试者中的群体药代动力学、药代动力学 - 药效学（抗FXa活性）以及暴露 - 反应（出血和血栓栓塞二元终点）进行了表征。阿哌沙班的药代动力学通过具有一级吸收和消除的二室模型得到充分表征。年龄、性别和亚洲种族对暴露的影响小于25%，而预计重度肾功能损害受试者的暴露量比参考受试者（60岁、非亚洲男性、体重85 kg、肌酐清除率为100 mL/min）高56%。阿哌沙班浓度与抗FXa活性之间的关系通过斜率估计为0.0159 IU/ng的线性模型描述。发生出血或血栓栓塞事件的受试者数量较少，通过逻辑回归分析未发现阿哌沙班暴露与临床终点之间存在统计学上的显著关系。
