Minase Research Institute, Ono Pharmaceutical Co., Ltd., 3-1-1, Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
Preclinical Research Unit, Sumitomo Dainippon Pharma Co., Ltd., 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-0022, Japan.
J Pharm Sci. 2020 Mar;109(3):1403-1416. doi: 10.1016/j.xphs.2019.12.009. Epub 2019 Dec 18.
The purpose of the present study was to characterize current biopharmaceutics modeling and simulation software regarding the prediction of the fraction of a dose absorbed (Fa) in humans. As commercial software products, GastroPlus™ and Simcyp® were used. In addition, the gastrointestinal unified theoretical framework, a simple and publicly accessible model, was used as a benchmark. The Fa prediction characteristics for a total of 96 clinical Fa data of 27 model drugs were systematically evaluated using the default settings of each software product. The molecular weight, dissociation constant, octanol-water partition coefficient, solubility in biorelevant media, dose, and particle size of model drugs were used as input data. Although the same input parameters were used, GastroPlus™, Simcyp®, and the gastrointestinal unified theoretical framework showed different Fa prediction characteristics depending on the rate-limiting steps of oral drug absorption. The results of the present study would be of great help for the overall progression of physiologically based absorption models.
本研究的目的是描述当前的生物药剂学建模和模拟软件在预测人体吸收分数 (Fa) 方面的特点。选择 GastroPlus™ 和 Simcyp® 这两种商业软件产品，并使用简单且公开的胃肠道统一理论框架作为基准。使用每种软件产品的默认设置，系统地评估了总共 96 种 27 种模型药物的临床 Fa 数据的 Fa 预测特征。模型药物的分子量、离解常数、辛醇-水分配系数、生物相关介质中的溶解度、剂量和粒径用作输入数据。尽管使用了相同的输入参数，但 GastroPlus™、Simcyp® 和胃肠道统一理论框架根据口服药物吸收的限速步骤显示出不同的 Fa 预测特征。本研究的结果将对生理吸收模型的整体进展有很大帮助。
