THE IMPROVED EVERTED GUT SAC - A SIMPLE METHOD TO STUDY INTESTINAL P-GLYCOPROTEIN

P-glycoprotein (P-gp) is an energy-dependent transporter protein locat ed in the apical membrane of intestinal mucosal cells. It is believed that it may limit the bioavailability of many orally administered drug s, by transporting them back into the intestinal lumen following their absorption by the enterocytes. To demonstrate the activity of the int estinal P-gp in vitro, we have used the 'improved' rat everted gut sac system, where good tissue viability and metabolic activity is maintai ned by incubating the everted sacs in tissue culture medium. Digoxin w as used as the test drug. After 90 min incubation, its transport acros s the intestinal mucosa was enhanced 2.5-fold by the P-gp inhibitor ve rapamil, and 5-fold by the inhibitor quinidine. In the presence of the three drugs, the sacs showed uniform kinetics and good viability, as assessed by the active transport of glucose and lack of release of cel lular enzymes. The improved everted gut sac system has potential as a simple and efficient tool to evaluate the role of P-gp in the intestin al absorption of drugs, and to screen for putative P-gp inhibitors tha t may improve the bioavailability of drugs susceptible to transport by P-gp. (C) 1998 Elsevier Science B.V. All rights reserved.