Prediction characteristics of oral absorption simulation software evaluated using structurally diverse low solubility drugs

Authors: Matsumura N, Hayashi S, Akiyama Y, Ono A, Funaki S, Tamura N, Kimoto T, Jiko M, Haruna Y, Sarashina A, Ishida M, Nishiyama K, Fushimi M, Kojima Y, Yoneda K, Nakanishi M, Kim S, Fujita T, Sugano K
Publication: J Pharm Sci
Keywords: biopharmaceutics, dissolution, gastroplus, mechanistic absorption modeling, oral absorption, pbbm, PBPK modeling, permeability, physiologically based pharmacokinetic modeling, simulation
Software: GastroPlus®

Abstract

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, GastroPlusTM and SimCYP® were employed. In addition, the gastrointestinal unified theoretical (GUT) framework, a simple and publicly accessible model, was employed 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. Even though the same input parameters were used, GastroPlusTM, SimCYP® and the GUT 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.