The improved everted gut sac: a simple method to study intestinal P-glycoprotein

Abstract

P-glycoprotein (P-gp) is an energy-dependent transporter protein located in the apical membrane of intestinal mucosal cells. It is believed that it may limit the bioavailability of many orally administered drugs, by transporting them back into the intestinal lumen following their absorption by the enterocytes. To demonstrate the activity of the intestinal P-gp in vitro, we have used the `improved' rat everted gut sac system, where good tissue viability and metabolic activity is maintained by incubating the everted sacs in tissue culture medium. Digoxin was used as the test drug. After 90 min incubation, its transport across the intestinal mucosa was enhanced 2.5-fold by the P-gp inhibitor verapamil, 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 cellular enzymes. The improved everted gut sac system has potential as a simple and efficient tool to evaluate the role of P-gp in the intestinal absorption of drugs, and to screen for putative P-gp inhibitors that may improve the bioavailability of drugs susceptible to transport by P-gp.