Global Product Development Clinical Pharmacology, Pfizer Inc., MS 8260-2212, Eastern Point Road, Groton, CT, 06340, USA.
Clinical Pharmacology and Pharmacometrics, Discovery Medicine and Clinical Pharmacology, Bristol-Myers Squibb Company, Princeton, NJ, USA.
Clin Pharmacokinet. 2019 Oct;58(10):1265-1279. doi: 10.1007/s40262-019-00775-z.
Apixaban is an oral, direct factor Xa inhibitor that inhibits both free and clot-bound factor Xa, and has been approved for clinical use in several thromboembolic disorders, including reduction of stroke risk in non-valvular atrial fibrillation, thromboprophylaxis following hip or knee replacement surgery, the treatment of deep vein thrombosis or pulmonary embolism, and prevention of recurrent deep vein thrombosis and pulmonary embolism. The absolute oral bioavailability of apixaban is ~ 50%. Food does not have a clinically meaningful impact on the bioavailability. Apixaban exposure increases dose proportionally for oral doses up to 10 mg. Apixaban is rapidly absorbed, with maximum concentration occurring 3-4 h after oral administration, and has a half-life of approximately 12 h. Elimination occurs via multiple pathways including metabolism, biliary excretion, and direct intestinal excretion, with approximately 27% of total apixaban clearance occurring via renal excretion. The pharmacokinetics of apixaban are consistent across a broad range of patients, and apixaban has limited clinically relevant interactions with most commonly prescribed medications, allowing for fixed dosages without the need for therapeutic drug monitoring. The pharmacodynamic effect of apixaban is closely correlated with apixaban plasma concentration. This review provides a summary of the pharmacokinetic, pharmacodynamic, biopharmaceutical, and drug-drug interaction profiles of apixaban. Additionally, the population-pharmacokinetic analyses of apixaban in both healthy subjects and in the target patient populations are discussed.
阿哌沙班是一种口服、直接的 Xa 因子抑制剂，可同时抑制游离和结合型的 Xa 因子，已被批准用于多种血栓栓塞性疾病的临床治疗，包括降低非瓣膜性心房颤动患者的中风风险、髋关节或膝关节置换术后的血栓预防、深静脉血栓或肺栓塞的治疗，以及预防复发性深静脉血栓和肺栓塞。阿哌沙班的绝对口服生物利用度约为 50%。食物对其生物利用度没有临床意义上的影响。口服剂量达 10mg 时，阿哌沙班暴露量呈剂量比例增加。阿哌沙班吸收迅速，口服后 3-4 小时达最大血药浓度，半衰期约为 12 小时。消除途径包括代谢、胆汁排泄和直接肠道排泄，约 27%的阿哌沙班总清除率通过肾脏排泄。阿哌沙班在广泛的患者人群中具有一致的药代动力学特征，与大多数常用药物的临床相关相互作用有限，允许使用固定剂量，无需进行治疗药物监测。阿哌沙班的药效学作用与阿哌沙班的血浆浓度密切相关。本文综述了阿哌沙班的药代动力学、药效学、生物药剂学和药物相互作用特征。此外，还讨论了阿哌沙班在健康受试者和目标患者人群中的群体药代动力学分析。
