Effects of NSAIDS and PGE ₁ analogue on the permeability of human small intestine

We studied permeability of human small intestine to clarify the following questions. 1) Does indomethacin increase intestinal permeability (IP)? 2) Does ornoprostil (PGE ₁ analogue) prevent the increased IP due to indomethacin? 3) Does acemetacin (pro-drug) increase IP? Eleven healthy volunteers were studied before and after ingestion of indomethacin, acemetacin, ornoprostil. After an overnight fast, they drank an isotonic solution containing 1.5 g rhamnose and 10.5 g lactulose. IP was estimated with lactulose/rhamnose percentage excretion in urine for 5 hours. An administration of indomethacin (75 mg) for one day increased IP significantly, and the coadministration of indomethacin and ornoprostil showed no significant change in IP compared with those of controls. Pro-drug administration did not increase IP. It is suggested that simultaneous administration of ornoprostil prevent the mucosal damage caused by indomethacin clinically, and that the mechanism of this increase IP is due to lack of mucosal prostaglandins on the small intestine.