Abstract：
Advanced compartmental absorption and transit (ACAT) based computational models have become increasingly popular in the industry for predicting oral drug product performance. However, due to its complexity, some compromises have been made in practice, and the stomach is often assigned as a single compartment. Although this assignment worked generally, it may not be sufficient to reflect the complexity of the gastric environment under certain conditions. For example, this setting was found to be less accurate in estimating stomach pH and solubilization of certain drugs under food intake, which leads to a misprediction of the food effect. To overcome the above, we explored the use of a kinetic pH calculation (KpH) for the single-compartment stomach setting. Several drugs have been tested with the KpH approach and compared with the default setting of Gastroplus. In general, the Gastroplus prediction of food effect is greatly improved, suggesting this approach is effective in improving the estimation of physicochemical properties related to food effect for several basic drugs by Gastroplus.
摘要：
基于先进的隔室吸收和转运(ACAT)的计算模型在预测口服药物产品性能的行业中变得越来越流行。然而,由于其复杂性，在实践中做出了一些妥协，胃通常被分配为一个单独的隔间。尽管这项任务总体上奏效了，它可能不足以反映某些条件下胃环境的复杂性。例如,发现这种设置在估计食物摄入下的胃pH值和某些药物的溶解方面不太准确，这导致了对食物效果的错误预测。为了克服上述问题，我们探索了在单室胃设置中使用动力学pH计算（KpH）。已经用KpH方法测试了几种药物，并与Gastroplus的默认设置进行了比较。总的来说,Gastroplus对食物效果的预测大大提高，表明这种方法可以有效地改善Gastroplus对几种基本药物与食物效应相关的理化性质的估计。
