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

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.

Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Study flow chart and demographics of participants in colesevelam study

Figure 2

Effects of NaCDC on colonic transit (GC) at 24 and 48 hours, and stool form and frequency. Data show least square means ± SEM. Note that there is an overall acceleration of colonic transit, and this is significantly greater with the 1000 mg dose of Na CDC (p

Figure 3

Effects of placebo or colesevelam on overall colonic transit at 24 hours in individual patients. Note that 7/12 participants in the colesevelam arm had reduced colonic transit by >0.7. The lines link the transit results at baseline and post-treatment.

Figure 4

Effects of colesevelam and placebo on ascending colon emptying t1/2 in relation to the rank of baseline fasting serum 7αC4. Note that the relationship between baseline fasting serum 7αC4 and ascending colon emptying times was positive in patients on colesevelam treatment, but negative in patients on placebo, implying that treatment effects were enhanced by 7αC4 on active drug, but not on placebo. Solid lines represent the regression lines (predicted value for a given X-axis value), dashed lines are the 95% confidence limits for the regression lines, and the dotted lines represent the prediction or tolerance limits for the regression lines.