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

✍ Scribed by Catherine Pontier; Jean Pachot; Roger Botham; Bernard Lenfant; Philippe Arnaud

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 410 KB
• Volume: 90
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.1111

✦ Synopsis

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 absorption in humans was compared. Similar apparent permeability values (log P app ) were obtained in both models for the majority of compounds tested, and plots of log P app versus fraction absorbed in humans gave comparable sigmoidal curves. A linear correlation was also observed between the log P app values derived from these two models, which suggests that HT29-MTX is an alternative model for absorption prediction in humans. The similarity of both the diffusion coef®cients and permeability values obtained for a range of hydrophilic and lipophilic compounds in the two models indicates that the mucus layer secreted by the human adenocarcinoma HT29-MTX goblet cells does not constitute a diffusion barrier to such compounds. The lack of P-glycoprotein (P-gp) in the HT29-MTX cell line may explain the higher permeability values obtained for cimetidine and sumatriptan in this model compared with those derived from the Caco-2/TC7 monolayers. The results suggest that the HT29-MTX model can be used to rank order the passive permeability of compounds, irrespective of their potential interaction with P-gp, which may facilitate optimization of the physicochemical features of compounds within a chemical series.