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 logP app values of a secondary set of 34 compounds were correlated with the measured values. Under the medicinal logP 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.