Effects of Chenodeoxycholate and a Bile Acid Sequestrant, Colesevelam, on Intestinal Transit and Bowel Function

Suwebatu T. Odunsi-Shiyanbade, Michael Camilleri, Sanna McKinzie, Duane Burton, Paula Carlson, Irene A. Busciglio, Jesse Lamsam, Ravinder Singh, Alan R. Zinsmeister

Research output: Contribution to journalArticlepeer-review

113 Scopus citations

Abstract

Background & Aims: Di-α hydroxy bile salt, sodium chenodeoxycholate (CDC), and bile acid binding have unclear effects on colonic transit in health and disease. Methods: We performed 2 randomized, double-blind, placebo-controlled studies. In healthy volunteers (20 per group), we evaluated the effects of oral placebo, 500 mg, or 1000 mg of CDC (delayed-release, each given for 4 days) on gastrointestinal and colonic transit. A second trial compared the effects of colesevelam (1.875 g, twice daily) versus placebo in 24 patients (12 per group) with diarrhea-predominant irritable bowel syndrome (IBS-D) on transit, daily bowel frequency and consistency, and colonic mucosal permeability. Serum fasting 7α-hydroxy-4-cholesten-3-one (7αC4) was measured to screen for bile acid malabsorption. Effects of treatments on transit were compared using analysis of covariance with body mass index and 7αC4 as covariates. Results: In healthy volunteers, CDC significantly accelerated colonic transit (at 24 and 48 hours, P = .01 and P < .0001, respectively), increased stool frequency and ease of passage (both P < .001), and evacuation (P = .02), and decreased stool consistency (P < .001). Four of the 24 IBS-D patients had increased serum 7αC4 levels. In IBS-D, colesevelam modestly affected overall colonic transit (24 h; P = .22). Emptying of the ascending colon took an average of 4 hours longer in patients given colesevelam compared with placebo; treatment effect was associated with baseline serum 7αC4 levels (P = .0025). Colesevelam was associated with greater ease of stool passage (P = .048) and somewhat firmer stool consistency (P = .12). No effects on mucosal permeability or safety were identified. Conclusions: Sodium chenodeoxycholate in health and colesevelam in IBS-D patients have opposite effects on colonic transit and fecal parameters.

Original languageEnglish (US)
Pages (from-to)159-165.e5
JournalClinical Gastroenterology and Hepatology
Volume8
Issue number2
DOIs
StatePublished - Feb 2010

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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