Department of Internal Medicine, Division of Rheumatology, University of Michigan.
Department of Clinical Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
Curr Opin Rheumatol. 2021 May 1;33(3):221-232. doi: 10.1097/BOR.0000000000000799.
Although mycophenolate mofetil (MMF) has been used successfully to treat a myriad of autoimmune diseases, its complex pharmacokinetics make it difficult to determine the true drug exposure for an individual patient. This review summarizes the body of literature focused on the gold standard measurement of the area under the curve (AUC) of mycophenolic acid (MPA), the active metabolite of MMF.
Fixed dosing of MMF leads to highly variable drug exposure. Retrospective series have reported improved clinical outcomes when a minimum AUC value from 0 to 12 h (AUC0-12h) ≥30 mg h/l is achieved. MPA levels are affected by various drug interactions, hypoalbuminemia, and renal insufficiency and the measurement of free rather than total MPA levels is prudent in some situations. A limited number of studies employing prospective dose adjustment of MMF based on AUC0-12h measurements have yielded mixed results.
Given the wide range of MPA AUC encountered in autoimmune diseases, dose adjustments of MMF based on AUC rather than fixed dosing of MMF should be considered in both clinical practice and clinical trials. Limited sampling strategies have been proposed to improve clinical feasibility of measurements, but a standard is yet to be defined.
霉酚酸酯(MMF)已成功用于治疗多种自身免疫性疾病,但由于其复杂的药代动力学,难以确定个体患者的真实药物暴露情况。本文综述了关注霉酚酸(MMF 的活性代谢物)的曲线下面积(AUC)的金标准测量的文献。
MMF 的固定剂量导致药物暴露高度可变。回顾性系列报告称,当达到 0 至 12 小时 AUC 值(AUC0-12h)≥30mg h/l 时,临床结局得到改善。MPA 水平受多种药物相互作用、低白蛋白血症和肾功能不全的影响,在某些情况下,测量游离而非总 MPA 水平更为谨慎。少数基于 AUC0-12h 测量的前瞻性 MMF 剂量调整研究得出了混合结果。
鉴于在自身免疫性疾病中遇到的 MPA AUC 范围很广,应考虑根据 AUC 而不是 MMF 的固定剂量调整 MMF 的剂量,无论是在临床实践中还是临床试验中。已经提出了有限的采样策略来提高测量的临床可行性,但尚未定义标准。