Almalbis Christian Andrew, Md Redzuan Adyani, Andrada Chester Paul, Gonzaga Nicole Ann, Mohd Saffian Shamin
Center for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; Department of Pharmacy, College of Pharmacy and Medical Technology, University of San Agustin, Iloilo City, Philippines.
Center for Quality Management of Medicines, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
J Thromb Haemost. 2025 Apr;23(4):1289-1314. doi: 10.1016/j.jtha.2024.12.032. Epub 2025 Jan 9.
Apixaban and rivaroxaban are activated factor X (FXa) inhibitors commonly used for treatment of venous thromboembolism and stroke prevention in patients with atrial fibrillation. While routine monitoring of their concentrations is not recommended, but it may be beneficial in certain situations. Expected peak and trough concentrations remain poorly understood, with most data derived from small studies.
To establish the average peak and trough concentrations of apixaban and rivaroxaban from real-world studies.
PubMed, Scopus, and Web of Science were searched until October 2023 for observational studies reporting apixaban and rivaroxaban concentrations. Meta-regression was used to examine factors influencing these concentrations.
Sixteen studies involving 1054 apixaban and 1321 rivaroxaban patients were pooled using random-effects model. Mean apixaban peak concentrations were 157 ng/mL (95% CI, 127-187) for 2.5 mg and 228 ng/mL (95% CI, 204-252) for 5 mg, with trough concentrations of 77 ng/mL (95% CI, 56-98) and 113 ng/mL (95% CI, 101-124), respectively. Mean rivaroxaban peak concentrations were 168 ng/mL (95% CI, 104-232) for 10 mg, 225 ng/mL (95% CI, 192-257) for 15 mg, and 229 ng/mL (95% CI, 193-264) for 20 mg, with trough concentrations of 23 ng/mL (95% CI, 13-32), 31 ng/mL (95% CI, 26-36), and 36 ng/mL (95% CI, 25-47), respectively. Meta-regression revealed age and creatinine clearance correlated with apixaban peak concentrations. Creatinine clearance correlated with apixaban and rivaroxaban trough concentrations.
The pooled mean concentrations align with expected concentration ranges reported in different pharmacokinetic studies.
阿哌沙班和利伐沙班是常用的活化X因子（FXa）抑制剂，用于治疗静脉血栓栓塞症和预防心房颤动患者的中风。虽然不建议常规监测它们的浓度，但在某些情况下可能有益。预期的峰浓度和谷浓度仍知之甚少，大多数数据来自小型研究。
通过真实世界研究确定阿哌沙班和利伐沙班的平均峰浓度和谷浓度。
检索PubMed、Scopus和Web of Science数据库至2023年10月，查找报告阿哌沙班和利伐沙班浓度的观察性研究。采用Meta回归分析影响这些浓度的因素。
使用随机效应模型汇总了16项研究，涉及1054例阿哌沙班患者和1321例利伐沙班患者。2.5mg阿哌沙班的平均峰浓度为157ng/mL（95%CI，127 - 187），5mg的为228ng/mL（95%CI，204 - 252），谷浓度分别为77ng/mL（95%CI，56 - 98）和113ng/mL（95%CI，101 - 124）。10mg利伐沙班的平均峰浓度为168ng/mL（95%CI，104 - 232），15mg的为225ng/mL（95%CI，192 - 257），20mg的为229ng/mL（95%CI，193 - 264），谷浓度分别为23ng/mL（95%CI，13 - 32）、31ng/mL（95%CI，26 - 36）和36ng/mL（95%CI，25 - 47）。Meta回归显示年龄和肌酐清除率与阿哌沙班峰浓度相关。肌酐清除率与阿哌沙班和利伐沙班的谷浓度相关。
汇总的平均浓度与不同药代动力学研究报告的预期浓度范围一致。
