ANTISECRETORY ACTIVITIES OF ORALLY-ADMINISTERED LOPERAMIDE AND LOPERAMIDE OXIDE ON INTESTINAL SECRETION IN RATS

In-vivo experiments in the rat jejunum have been performed to compare the antisecretory effect of orally administered loperamide with the ef fect of its pro-drug, loperamide oxide. Both loperamide and loperamide oxide, administered orally, reduced the secretory effect of prostagla ndin E2 (32 ng min-1, intra-arterially) in the jejunum and the colon. Differences between the two drugs as to time course and dose response can be seen. Loperamide oxide shows its antisecretory effect in the je junum. and at a dose of 2 mg kg-1 also shows its effect in the colon 1 h after administration. The effect was maximal after 2 h and decrease d after 4 h. A dose-response relationship was demonstrated at 2 h in t he jejunum and the colon. In comparison, the effect of loperamide star ted later, and a good dose-response relationship was not observed in t he jejunum or in the colon, higher doses always appearing less effecti ve than lower doses.