Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
Clin Pharmacol Drug Dev. 2022 Nov;11(11):1331-1340. doi: 10.1002/cpdd.1141. Epub 2022 Aug 31.
Meal timings and content related to gallbladder emptying in the enterohepatic circulation are important for explaining the high variability in mycophenolic acid exposure. The limited sampling strategy (LSS) was established to estimate the area under the plasma concentration-time curve from time 0 to 12 hours (AUC ) of mycophenolic acid in therapeutic drug monitoring. The aim of this study is to investigate the effect of meal timings and content on the AUC of mycophenolic acid and to assess the influence of meals on LSS. A mycophenolic acid pharmacokinetic model with a mechanism-based enterohepatic circulation process was employed to perform simulations under various assumed meal scenarios. The simulations were compared to evaluate the effect of meal timings and meal content on mycophenolic acid AUC . Monte Carlo simulations were performed using the meal parameter with the greatest impact on mycophenolic acid AUC as a variable. The corresponding LSS equations were established, and the predictive performance was assessed. Both the meal timings and meal content affected the mycophenolic acid AUC , and the postdose fasting period had the greatest impact. The predictive performance of the LSS is sensitive to the postdose fasting period. Therefore, meal timings may improve the estimation of mycophenolic acid AUC and the efficacy of therapeutic drug monitoring.
饮食时间和内容与肠肝循环中胆囊排空有关，对于解释麦考酚酸暴露的高度变异性很重要。有限采样策略（LSS）被建立用于估计治疗药物监测中麦考酚酸从 0 到 12 小时的血浆浓度-时间曲线下面积（AUC）。本研究旨在探讨饮食时间和内容对麦考酚酸 AUC 的影响，并评估饮食对 LSS 的影响。采用基于机制的肠肝循环过程的麦考酚酸药代动力学模型，在各种假定的饮食情况下进行模拟。模拟结果进行比较，以评估饮食时间和饮食内容对麦考酚酸 AUC 的影响。使用对麦考酚酸 AUC 影响最大的饮食参数作为变量进行蒙特卡罗模拟。建立了相应的 LSS 方程，并评估了预测性能。饮食时间和饮食内容均影响麦考酚酸 AUC，而餐后禁食期影响最大。LSS 的预测性能对餐后禁食期敏感。因此，饮食时间可能会改善麦考酚酸 AUC 的估计和治疗药物监测的疗效。
