Internal Medicine, Medical affairs, Pfizer, New York, NY, 10017, USA.
Global Product Development, Clinical Pharmacology, Pfizer, Groton, CT, 06340, USA.
Am J Cardiovasc Drugs. 2022 Nov;22(6):615-631. doi: 10.1007/s40256-022-00524-x. Epub 2022 May 16.
Relatively little is known about the influence of extreme body weight on the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety of drugs used in many disease states. While direct oral anticoagulants (DOACs) have an advantage over warfarin in that they do not require routine drug monitoring, some may regard this convenience as less compelling in obese patients. Some consensus guidelines discourage using DOACs in patients weighing > 120 kg or with a body mass index > 35-40 kg/m, given a sparsity of available data in this population and the concern that fixed dosing in obese patients might lead to decreased drug exposure and lower efficacy. Per the prescribing information, apixaban does not require dose adjustment in patients weighing above a certain threshold (e.g., ≥ 120 kg). Data from healthy volunteers and patients with nonvalvular atrial fibrillation (NVAF) or venous thromboembolism (VTE) have shown that increased body weight has a modest effect on apixaban's PK. However, the paucity of exposure data in individuals > 120 kg and the lack of guideline consensus on DOAC use in obese patients continue to raise concerns about potential decreased drug exposure at extreme weight. This article is the first to comprehensively review the available PK data in obese individuals without NVAF or VTE, and PK, PD, efficacy, effectiveness, and safety data for apixaban in obese patients with either NVAF or VTE, including subgroup analyses across randomized controlled trials and observational (real-world) studies. These data suggest that obesity does not substantially influence the efficacy, effectiveness, or safety of apixaban in these patients. Trial Registration ARISTOTLE: NCT00412984; AVERROES: NCT00496769; AMPLIFY: NCT00643201; AMPLIFY-EXT: NCT00633893; ADVANCE-1: NCT00371683; ADVANCE-2: NCT00452530; ADVANCE-3: NCT00423319 Apixaban Use in Obese Patients: A Review of the Pharmacokinetic, Interventional, and Observational Study Data (MP4 161.22 MB).
关于体重极端变化对药物药代动力学（PK）、药效学（PD）、疗效和安全性的影响，我们知之甚少。尽管直接口服抗凝剂（DOAC）相对于华法林具有优势，因为它们不需要常规药物监测，但有些人可能认为在肥胖患者中，这种便利性不那么重要。一些共识指南不建议在体重 > 120 公斤或体重指数 > 35-40 公斤/平方米的患者中使用 DOAC，因为在该人群中可用数据很少，而且担心在肥胖患者中固定剂量可能会导致药物暴露减少和疗效降低。根据说明书，阿哌沙班在体重超过一定阈值（例如，≥ 120 公斤）的患者中不需要调整剂量。来自健康志愿者和非瓣膜性心房颤动（NVAF）或静脉血栓栓塞（VTE）患者的数据表明，体重增加对阿哌沙班的 PK 有适度影响。然而，在体重 > 120 公斤的个体中，暴露数据很少，肥胖患者使用 DOAC 的指南共识缺乏，这仍然引起了对药物暴露潜在降低的担忧。本文是第一篇全面综述无 NVAF 或 VTE 的肥胖个体中可用 PK 数据，以及肥胖患者中 NVAF 或 VTE 患者的阿哌沙班 PK、PD、疗效、有效性和安全性数据，包括随机对照试验和观察性（真实世界）研究的亚组分析。这些数据表明，肥胖不会显著影响这些患者中阿哌沙班的疗效、有效性或安全性。试验注册 ARISTOTLE：NCT00412984；AVERROES：NCT00496769；AMPLIFY：NCT00643201；AMPLIFY-EXT：NCT00633893；ADVANCE-1：NCT00371683；ADVANCE-2：NCT00452530；ADVANCE-3：NCT00423319 阿哌沙班在肥胖患者中的应用：PK、干预和观察研究数据综述（MP4 161.22 MB）。
