Absorptive and motor components of the antidiarrhoeal action of loperamide: an in vivo study in pigs

Abstract

The effects of loperamide (0.1 mg/kg orally) on net colonic water absorption, orocolonic transit time, and intestinal motility were investigated in pigs chronically fitted either with two cannulas in the proximal colon and a catheter in the duodenum and the ileum or with intraparietal electrodes on the duodenum, jejunum, caecum, and proximal colon and a duodenal catheter. Loperamide, given 20 minutes before a meal reduced significantly colonic net water absorption for 10 hours after eating. It also reduced colonic flow rate, increased orocolonic transit time, modified the postprandial intestinal motility by inducing supplementary phase 3 motor complexes and did not affect caecocolonic motility. Intraduodenal infusion of a hypertonic solution of mannitol (900 mOsm/l; 0.6 ml/minute) for the first postprandial hour strongly reduced or reversed net colonic water absorption, increased the colonic flow rate, accelerated the orocolonic transit, and induced profuse diarrhoea. After loperamide administration, all these effects were blocked and the relative colonic water absorption, expressed as the fraction of flow entering the colon, was strongly increased. Mannitol did not modify motility of the small and large intestine, and supplementary phase 3 motor complexes were observed when mannitol infusion was preceded by loperamide administration. It is concluded that in experimental osmotic diarrhoea loperamide causes a reduction in digesta flow entering into the colon, mediated by its action on small intestinal motility, and an increase in colonic water absorption.