Comparison of the antisecretory effects of loperamide and loperamide oxide in the jejunum and the colon of rats in-vivo.

The antidiarrhoeal effect of loperamide is caused by its antimotility and antisecretory properties. In-vivo experiments in the rat jejunum and colon have been performed to compare the antisecretory effect of loperamide with the effect of its prodrug, loperamide oxide. Both loperamide and loperamide oxide administered intraluminally, equally and dose dependently (2 to 250 micrograms mL-1) reduced PGE2-induced net fluid secretion (32 ng min-1 i.a.) in the jejunum and colon. The antisecretory effect of both drugs is blocked by naloxone (1 mg kg-1 s.c.). It is concluded that loperamide oxide administered intraluminally is reduced to loperamide and has the same antisecretory potency as loperamide in jejunum and colon. The effect appears to be mediated via opiate receptors. The observation that loperamide cannot be detected in the colonic lumen two h after oral administration suggests that the drug is delivered from the blood stream to the site of action after absorption in the small intestine.