Institute of Pharmacy, Department of Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, Greifswald17489, Germany.
Mol Pharm. 2023 Feb 6;20(2):1039-1049. doi: 10.1021/acs.molpharmaceut.2c00782. Epub 2022 Dec 22.
Delayed gastric emptying is known to have a major impact on drug absorption. While the test meal recommended by the FDA and EMA to study food effects represents a worst-case scenario, it does not reflect the reality of the patients. Physiologically based pharmacokinetic (PBPK) models could bridge the gap between clinical settings of food effect studies and the diverse nonclinical situations by simulating the effect of meals with different compositions and volumes. A mathematical equation based on a stretched exponential function was reparameterized to describe the gastric emptying process of mixed solid meals. The model was fitted to literature data including the gastric emptying data of 23 meals from 15 studies. Using a multiple linear regression model, we were able to predict the two function parameters from the meal characteristics caloric content and the percentage of calories derived from fat. After implementation into the PBPK software PK-Sim, the model, together with a separate compartment for liquid gastric contents, was compared to commercially available software. The model is able to simulate the gastric emptying of mixed solid meals containing drugs based on specific meal characteristics. A second compartment allows for distribution between liquid and solid components and rapid gastric emptying along the .
已知胃排空延迟会对药物吸收产生重大影响。虽然 FDA 和 EMA 推荐的用于研究食物影响的测试餐代表了最坏的情况，但它并不能反映患者的实际情况。基于生理学的药代动力学（PBPK）模型可以通过模拟不同组成和体积的膳食来弥合食物效应研究的临床环境与各种非临床情况之间的差距。基于扩展指数函数的数学方程被重新参数化，以描述混合固体膳食的胃排空过程。该模型拟合了包括 15 项研究中的 23 个膳食的胃排空数据在内的文献数据。使用多元线性回归模型，我们能够从膳食特征（热量含量和脂肪热量百分比）预测两个函数参数。在将模型实现到 PBPK 软件 PK-Sim 中后，该模型与单独的液体胃内容物隔室一起与商业上可用的软件进行了比较。该模型能够基于特定的膳食特征模拟含有药物的混合固体膳食的胃排空。第二个隔室允许在液体和固体成分之间分配，并允许沿着. 快速排空。
