FLUX MEASUREMENTS ACROSS CACO-2 MONOLAYERS MAY PREDICT TRANSPORT IN HUMAN LARGE INTESTINAL TISSUE

Confluent monolayers of Caco-2 cells, a human colonic carcinoma cell l ine, have been used extensively to predict intestinal absorption. A di rect comparison of uptake characteristics, however, between cell monol ayers and human tissue is missing in the literature. We have determine d the flux for a series of small organic molecules, peptide and protei n therapeutics, across Caco-2 monolayers and normal human colonic and rectal tissue in vitro to assess whether or not a predictive correlati on of transport exists. Caco-2 cells were grown to confluency on Snapw ells, and human tissue was obtained from patients undergoing surgery f or localized tumors. Mucosa-serosa fluxes were measured by HPLC for sm all molecules and peptides, and proteins were analyzed by ELISA or RIA . Permeability coefficients were calculated from flux data and compare d with previously published coefficients where possible. The permeabil ity coefficients for the examined molecules were of a similar magnitud e across Caco-2 cell monolayers and human tissues, ranging from 10(-7) to 10(-5) cm/s. A best-fit analysis of a log-log plot of transport me asurements obtained in these two systems gave a good correlation (R(2) = 0.991). From this limited data set it appears that uptake character istics for human colon and rectum are similar to those of Caco-2 cell monolayers. Thus, flux measurements across Caco-2 monolayers may be pr edictive for permeabilities of human colon and rectum for different cl asses of therapeutics.