In Vitro Drug Absorption Models. II. Salicylate, Cefoxitin, α-Methyldopa and Theophylline Uptake in Cells and Rings: Correlation with In Vivo Bioavailability.

Isolated mucosal cells and everted intestinal rings have been examined as potential in vitro models for intestinal drug absorption. The uptake of salicylate, cefoxitin, α-methyldopa and theophylline was characterized on the basis of time, concentration and temperature dependence and compared to in vivo drug absorption. Theophylline was well absorbed in all systems. Biochemical studies supported a passive transport mechanism, although a significant temperature dependence was observed. Salicylate, cefoxitin and α-methyldopa demonstrated time- and concentration-dependent absorption. The uptake of α-methyldopa was temperature-dependent in both the isolated cell and ring studies. With all drugs, cellular uptake exhibited greater variability than drug accumulation in rings. A comparison of in vitro and in vivo absorption demonstrated a good correlation between the data from in vivo studies and intestinal rings. Cellular drug uptake did not completely mimic that observed in vivo. On the basis of technical aspects of preparation, reproducibility of results, and correlation with in vivo drug bioavailability, everted intestinal rings were judged to be the best in vitro model for intestinal drug absorption.