Effects of cisapride on gall bladder emptying, intestinal transit, and serum deoxycholate: a prospective, randomised, double blind, placebo controlled trial

Abstract

Background-Octreotide inhibits gall bladder emptying and prolongs intestinal transit. This leads to increases in the proportion of deoxycholic acid in, and cholesterol saturation of, gall bladder bile, factors that contribute to the pathogenesis of octreotide induced gall stones. Aims-To see if an intestinal prokinetic, cisapride, could overcome these adverse eVects of octreotide and if so, be considered as a candidate prophylactic drug for preventing iatrogenic gall bladder stones. Methods-A randomised, double blind, placebo controlled, crossover design was used to examine the eVects of cisapride (10 mg four times daily) on gall bladder emptying, mouth to caecum and large bowel transit times, and the proportions of deoxycholic acid and other bile acids, in fasting serum from: (i) control subjects (n=6), (ii) acromegalic patients not treated with octreotide (n=6), (iii) acromegalics on long term octreotide (n=8), and (iv) patients with constipation (n=8). Results-Cisapride had no prokinetic effect on the gall bladder. In fact, it significantly increased both fasting and postprandial gall bladder volumes. However, it shortened mouth to caecum (from 176 (13) to 113 (11) minutes; p<0.001) and large bowel (from 50 (3.0) to 31 (3.4) h; p<0.001) transit times. It also reduced the proportion of deoxycholic acid in serum from 26 (2.3) to 15 (1.8)% (p<0.001), with a reciprocal increase in the proportion of cholic acid from 40 (3.5) to 51 (3.8)% (p<0.01). There were significant linear relationships between large bowel transit time and the proportions of deoxycholic acid (r=0.81; p<0.001) and cholic acid (r=−0.53; p<0.001) in fasting serum. Interpretation/summary-Cisapride failed to overcome the adverse eVects of octreotide on gall bladder emptying but it countered octreotide induced prolongation of small and large bowel transit. Therefore, if changes in intestinal transit contribute to the development of octreotide induced gall bladder stones, enterokinetics such as cisapride may prevent their formation. (Gut 2001;49:828-834)

Augmented cholesterol absorption and sarcolemmal sterol enrichment slow small intestinal transit in mice, contributing to cholesterol cholelithogenesis

“…For this reason, we chose not to test other motility agonists, such as acetylcholine (Price et al 1969), since our results could be fully explained by CCK antagonism; moreover, a different ex vivo experimental set‐up would have been required. Nonetheless, as highlighted earlier, pro‐kinetic agents, including cisapride in humans (Veysey et al 2001) and erythromycin in ground squirrels (Xu et al 1998), reverse presumed cholesterol‐induced small intestinal hypomotility under these lithogenic conditions, indicating that other pro‐motility agents clearly function by CCK‐1R‐independent pathways.…”

Bile acid metabolism by fresh human colonic contents: a comparison of caecal versus faecal samples

“…To test the substrate-enzyme hypothesis (by studying the relationship between CA concentration and 7α-DH in the caecum), we were relying on spontaneous variations in caecal CA concentration, rather than on pharmacological manoeuvres designed to perturb the balance between CA and DCA by using broad spectrum antibiotics,8 29 drugs that increase or decrease the rates of transit through the intestine,30 31 or regimens that change intracolonic pH, such as oral lactulose 3233 Instead, we relied on spontaneous variations in “endogenous” caecal CA concentrations which, in the event, ranged from 0.14 to 1.65 μmol/ml although the explanation for this scatter in results is unknown.…”

Drugs Acting on the Gut: Prokinetics, Antispasmodics, Laxatives

“…Amplitude of esophageal peristalsis as well as resting LES tone is increased [ 72 ]. Cisapride also decreases mouth to cecum time and colonic transit time [ 73 ].…”