1995 Volume 10 Issue supplement Pages 68-71
Recently, Caco-2 monolayer has recieved considerable attention from the pharmaceutical industry because it may serve as a model for predicting oral drug absorption. In this report, Caco-2 monolayer was used to describe the oral absorption of (1) drugs which are absorbed via a carrier-mediated system, (2) an ester-type prodrug of anitibiotics, (3) peptide drugs which undergo the extensive degradation in the intestine. The result of each study was as follows: (1) The contribution of carrier-mediated transport to the total permeability of cephalexin to Caco-2 monolayer was much smaller than that to the rat jejunum obserbed in vivo. It was indicated that the prediction from the result of Caco-2 experiment might underestimate the oral absorption of cephalexin. (2) The enhanced oral absorption of cefotiam by its ester-type prodrug, cefotiam-hexetil, was well demonstrated in the in vitro experiment using Caco-2monolayer. Caco-2 monolayer was shown to have the similar esterase activity with that of a small intestine which cleaves the ester-bond of prodrug during the absorption. (3) The degradtion pattern of three peptides in the homogenate of Caco-2 cells are different from that in rat intestinal one, suggesting the inter-species difference of the mucosal peptid ase activity. The permeability of those peptides to Caco-2 monolayer was very low, thus, it was considered that the low pemeability, as well as the rapid degradation, was a main reason for their poor oral absorption. Finally, the effect of emulsion which solubilizes the high lipophlic drug on its oral absorption was studied using Caco-2 monolayer. From those results, the possibility and the limit of in vitro system using Caco-2 monolayer to predict the oral drug absorption were discussed.
