Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells.

A human intestinal cell line, Caco-2, was used as a model to study the passive diffusion of drugs across intestinal epithelium. The cells formed continuous monolayers when grown on permeable filters of polycarbonate. After 10 days in culture, the monolayers had a transmembrane resistance of approximately 260 ohms.cm2 and a cell density of 0.9 x 10(6) cells/cm2. At this time the cells were impermeable to [14C]polyethyleneglycol (MW 4000). These characteristics remained constant for 20 days (i.e., from day 10 to day 30). Six beta-blocking agents with a 2000-fold range of lipophilicity were studied for their transepithelial transport properties. The transport parameters were independent of drug concentration and transport direction. The apparent permeability coefficients ranged from 41.91 +/- 4.31 x 10(-6) cm/s for the most lipophilic drug, propranolol, to 0.203 +/- 0.004 x 10(-6) cm/s for the most hydrophilic drug, atenolol. The transport parameters were compared with those published for rat ileum. The transport rates were similar for four out of five drugs. Atenolol was transported at a slower rate in the Caco-2 model, which may be explained by the fact that the Caco-2 cells form a tighter epithelium than the rat ileal enterocytes. The findings of this paper indicate that Caco-2 cells may be used to model the intestinal absorption of drugs.