Daiichi Sankyo Co, Ltd, Nihonbashi-honcho, Chuo-ku, Tokyo, Japan.
Clin Pharmacol Drug Dev. 2017 Sep;6(5):484-491. doi: 10.1002/cpdd.329. Epub 2016 Dec 29.
This is a population pharmacokinetic (PopPK) analysis to predict PK of edoxaban, a direct-acting oral anticoagulant, in nonvalvular atrial fibrillation (NVAF) patients with severe renal impairment (SRI; creatinine clearance [CL ] <30 mL/min). Data from a phase 3 study recently conducted in Japanese NVAF patients (n = 90), including patients with SRI, were used to update the ENGAGE PopPK model that had been developed based on pooled data from the phase 3 ENGAGE AF-TIMI 48 study and 13 phase 1 PK studies, which included few patients with SRI. The final model indicated that the ENGAGE PopPK model was applicable to Japanese patients in that the model-simulated and study-observed concentration-time profiles were in agreement. Estimated model parameters after the addition of Japanese SRI data were consistent with those derived from the original ENGAGE PopPK data set. The model-predicted exposure in NVAF patients with SRI who received edoxaban at a 15-mg, once-daily dose was similar to that in patients with normal renal function or with mild renal impairment receiving a 30-mg dose. This suggests that efficacy and safety data from the ENGAGE AF study can be used to support dose setting for NVAF patients with SRI.
这是一项群体药代动力学（PopPK）分析，旨在预测直接口服抗凝剂依度沙班在伴有严重肾功能不全（SRI；肌酐清除率 [CL] <30 mL/min）的非瓣膜性心房颤动（NVAF）患者中的药代动力学。最近在日本 NVAF 患者（n=90）中进行的一项 3 期研究的数据被用于更新 ENGAGE PopPK 模型，该模型是基于 3 期 ENGAGE AF-TIMI 48 研究和 13 项 1 期 PK 研究的汇总数据开发的，这些研究中 SRI 患者较少。最终模型表明，ENGAGE PopPK 模型适用于日本患者，因为模型模拟和研究观察的浓度-时间曲线一致。在添加日本 SRI 数据后，估计的模型参数与原始 ENGAGE PopPK 数据集得出的参数一致。接受每日 15 毫克一次剂量的 SRI NVAF 患者的模型预测暴露量与肾功能正常或轻度肾功能不全接受 30 毫克剂量的患者相似。这表明，来自 ENGAGE AF 研究的疗效和安全性数据可用于支持 SRI NVAF 患者的剂量设定。
