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. (2020)

• Record Type: Journal Article
• Authors: Kamiya, Yusuke; Takaku, Hiroka; Yamada, Rio; Akase, Chisato; Abe, Yuto; Sekiguchi, Yuko; Murayama, Norie; Shimizu, Makiko; Kitajima, Masato; Shono, Fumiaki; Funatsu, Kimito; Yamazaki, Hiroshi
• Is Part Of: Toxicology reports. Volume 7(2020)
• Page Start: 149
• Page End: 154
• Publication Date: 2020
• Subjects: Caco-2 cells -- Octanol–water distribution coefficient -- Multivariate prediction equation -- Fraction absorbed -- No-observed-effect level; Toxicology -- Periodicals; Clinical toxicology -- Periodicals; Drug-Related Side Effects and Adverse Reactions; Hazardous Substances; Poisoning; Toxicology; Electronic journals; Periodicals; Periodicals; 571.9505
• DOI: 10.1016/j.toxrep.2020.01.004
• Languages: English
• ISSNs: 2214-7500

Abstract

Graphical abstract: Highlights: Permeability values of 90 industry chemicals were measured by a Caco-2 system. A multivariate prediction equation for permeability of chemicals was proposed. Chemical permeability coefficients were inversely associated with hepatic NOELs. Abstract: Apparent permeability coefficients ( P app ) 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 P app 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 log P app values of a secondary set of 34 compounds were correlated with the measured values. Under the medicinal log P app values associated with their reported fraction absorbed, a significant inverse non-linear correlation was found between the logarithmic transformed values of observed P app 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.