Determination and Prediction of Permeability across Intestinal Epithelial Cell Monolayer of a Diverse Range of Industrial Chemicals/Drugs for Estimation of Oral Absorption as a Putative Marker of Hepatotoxicity

Publication date: Available online 14 January 2020Source: Toxicology ReportsAuthor(s): Yusuke Kamiya, Hiroka Takaku, Rio Yamada, Chisato Akase, Yuto Abe, Yuko Sekiguchi, Norie Murayama, Makiko Shimizu, Masato Kitajima, Fumiaki Shono, Kimito Funatsu, Hiroshi YamazakiAbstractApparent permeability coefficients (Papp) across a human intestinal epithelial Caco-2 cell monolayer were measured for a range of industrial/drug chemicals. A predictive equation for determining in vitro Papp values of fifty-six substances was set up using multivariate regression analysis based on in silico-estimated physicochemical properties (molecular weights and water distribution coefficients for apical and basal pH environments) (r = 0.77, p <  0.01). Predicted logPapp values of a secondary set of 34 compounds were correlated with the measured values. Under the medicinal logPapp values associated with their reported fraction absorbed, a significant inverse non-linear correlation was found between the logarithmic transformed values of observed Papp values and reported hepatic no-observed-effect levels of industrial chemicals (r = –0.55, p <  0.01, n = 29). In vitro determination and/or in silico prediction of permeability across intestinal cells could be effective for estimating oral absorption as a putative indicator for hepatotoxicity.Graphical abstract
Source: Toxicology Reports - Category: Toxicology Source Type: research