Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function

Clin Gastroenterol Hepatol. 2010 Feb;8(2):159-65. doi: 10.1016/j.cgh.2009.10.020. Epub 2009 Oct 30.

Abstract

Background & aims: Di-alpha 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 7alpha-hydroxy-4-cholesten-3-one (7alphaC4) was measured to screen for bile acid malabsorption. Effects of treatments on transit were compared using analysis of covariance with body mass index and 7alphaC4 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 7alphaC4 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 7alphaC4 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adult
  • Allylamine / administration & dosage
  • Allylamine / analogs & derivatives*
  • Allylamine / therapeutic use
  • Chenodeoxycholic Acid / administration & dosage
  • Chenodeoxycholic Acid / therapeutic use*
  • Colesevelam Hydrochloride
  • Double-Blind Method
  • Female
  • Gastrointestinal Agents / administration & dosage
  • Gastrointestinal Agents / therapeutic use*
  • Gastrointestinal Transit / drug effects*
  • Humans
  • Intestines / physiology*
  • Male
  • Placebos / administration & dosage

Substances

  • Gastrointestinal Agents
  • Placebos
  • Chenodeoxycholic Acid
  • Allylamine
  • Colesevelam Hydrochloride