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 effect of its pro-drug, loperamide oxide. Both loperamide and loperamide oxide, administered orally, reduced the secretory effect of prostaglandin 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 jejunum, 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 decreased after 4 h. A dose-response relationship was demonstrated at 2 h in the jejunum and the colon. In comparison, the effect of loperamide started later, and a good dose-response relationship was not observed in the jejunum or in the colon, higher doses always appearing less effective than lower doses.