Department of Cardiology and Nephrology, Dokkyo Medical University, 880-Kitakobayashi, Mibu, Tochigi, 321-0293, Japan.
Internal Medicine, NHO Tochigi Medical Center, 1-10-37 Naka-Tomatsuri, Utsunomiya, Tochigi, 320-8580, Japan.
Drug Metab Pharmacokinet. 2020 Feb;35(1):151-159. doi: 10.1016/j.dmpk.2019.10.005. Epub 2019 Oct 25.
The anticoagulant actions of oral direct factor Xa (FXa) inhibitors can be inferred from their observed plasma concentrations; however, the steady-state pharmacokinetics (PK) of different FXa inhibitors have not been compared in clinically.
The sensitivity of the rivaroxaban, apixaban, and edoxaban in the STA-Liquid Anti-FXa assay were compared, and the anti-FXa plasma concentrations were measured for PK assessments. Nonlinear mixed-effects modeling was used to assess population PK in 329 patients with nonvalvular atrial fibrillation or venous thromboembolism. Patients were followed up for an average of 3.6 years.
Sensitivity was similar among the three drugs in this assay, which could directly compare plasma concentrations instead of anti-FXa activities. Overall exposure was greatest in 5 mg BID apixaban relative to other drugs (p < 0.001). The geometric mean AUC for the 0 to 24-h interval was 4550 ng h/mL for apixaban, 2710 ng h/mL for 15 mg QD rivaroxaban, and 1290 ng h/mL for 60 mg QD edoxaban. The PKs of 2.5 mg BID apixaban or 15 mg QD rivaroxaban were associated with hemorrhagic events.
Apixaban was associated with greater exposure, higher trough concentrations in plasma compared with rivaroxaban or edoxaban. Furthermore, a higher plasma concentration may partially predict hemorrhagic events.
口服直接因子 Xa（FXa）抑制剂的抗凝作用可以从其观察到的血浆浓度推断出来；然而，不同 FXa 抑制剂的稳态药代动力学（PK）尚未在临床上进行比较。
比较了利伐沙班、阿哌沙班和依度沙班在 STA-Liquid Anti-FXa 测定中的敏感性，并测量了抗-FXa 血浆浓度以进行 PK 评估。非线性混合效应模型用于评估 329 例非瓣膜性心房颤动或静脉血栓栓塞患者的群体 PK。患者平均随访 3.6 年。
在该测定中，这三种药物的敏感性相似，因此可以直接比较血浆浓度而不是抗-FXa 活性。与其他药物相比，5mg BID 阿哌沙班的总体暴露量最大（p<0.001）。阿哌沙班 0 至 24 小时间隔的几何平均 AUC 为 4550ng·h/mL，15mg QD 利伐沙班为 2710ng·h/mL，60mg QD 依度沙班为 1290ng·h/mL。2.5mg BID 阿哌沙班或 15mg QD 利伐沙班的 PK 与出血事件相关。
与利伐沙班或依度沙班相比，阿哌沙班的暴露量更大，血浆中的谷浓度更高。此外，较高的血浆浓度可能部分预测出血事件。
