HT29-MTX and Caco-2/TC7 monolayers as predictive models for human intestinal absorption: Role of the mucus layer

The permeability of 19 compounds in both the Caco-2/TC7 and HT29-MTX models was determined, and the ability of each model to predict intestinal absorp tion in humans was compared. Similar apparent permeability values (log P-ap p) were obtained in both models for the majority of compounds tested, and p lots of log P-app, versus fraction I absorbed in humans gave comparable sig moidal curves. A linear correlation was a so observed between the log P-app values derived from these two models, which suggests that HT29-MTX is an a lternative model for absorption prediction in humans. The similarity of bot h the diffusion coefficients and permeability values obtained for a range o f hydrophilic and lipophilic compounds in the two models indicates that the mucus layer secreted by the human adenocarcinoma HT29-MTX goblet cells doe s not constitute a diffusion barrier to such compounds. The lack of P-glyco protein (P-gp) in the HT29-MTX cell line may explain the higher permeabilit y values obtained for cimetidine and sumatriptan in this model compared wit h those derived from the Caco-2/TC7 monolayers. The results suggest that th e HT29-MTX model can be used to rank order the passive permeability of comp ounds, irrespective of their potential interaction with P-gp, which may fac ilitate optimization of the physicochemical features of compounds within a chemical series. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association.