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

Clin Gastroenterol Hepatol. 2009 Oct 29;

Authors: Odunsi-Shiyanbade ST, Camilleri M, McKinzie S, Burton D, Carlson P, Busciglio IA, Lamsam J, Singh R, Zinsmeister AR

BACKGROUND & AIMS:: Di- hydroxy bile salt, sodium chenodeoxycholate (CDC), and bile acid (BA) 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/group), we evaluated 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 (1.875g , twice daily) vs placebo in 24 patients (12/group) with diarrhea-predominant irritable bowel syndrome (IBS-D) on transit, daily bowel frequency and consistency, and colonic mucosal permeability. Serum fasting 7alphaC4 was measured to screen for BA malabsorption. Effects of treatments on transit were compared using analysis of covariance with body mass index (BMI) and 7alphaC4 as covariates. RESULTS:: In healthy volunteers, CDC significantly accelerated colonic transit (at 24h and 48h, p=0.01 and p<0.0001, respectively), increased stool frequency, ease of passage (both p<0.001), and evacuation (p=0.02), and decreased stool consistency (p<0.001). Four of the 24 IBS-D patients had increased serum 7alphaC4. In IBS-D, colesevelam modestly affected overall colonic transit (24h, p=0.22). Emptying of the ascending colon took an average 4 hours longer in patients given colesevelam compared to placebo; treatment effect was associated with baseline serum 7alphaC4 (p=0.0025). Colesevelam was associated with greater ease of stool passage (p=0.048) and somewhat firmer stool consistency (p=0.12). 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.

PMID: 19879973 [PubMed - as supplied by publisher]

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