Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome

Aliment Pharmacol Ther. 2015 Mar;41(5):438-48. doi: 10.1111/apt.13065. Epub 2015 Jan 16.

Abstract

Background: About one-third of patients with IBS-diarrhoea (irritable bowel syndrome-D) have evidence of increased bile acid synthesis or excretion.

Aims: To assess effects of the bile acid sequestrant, colesevelam, on faecal excretion of BAs, hepatic BA synthesis and diarrhoea in IBS-D; to appraise whether individual or random stool samples accurately reflect 48-h total faecal bile acid excretion and proportions of the main bile acids excreted and to study the faecal fat excretion in response to colesevelam.

Methods: A single-centre, unblinded, single-dose trial of effects of colesevelam, 1875 mg [3 tablets (625 mg tablets)] orally, twice daily, for 10 days on total 48-h faecal bile acid excretion and fasting serum C4 (7α-hydroxy-4-cholesten-3-one; surrogate of hepatic bile acid synthesis). Stool diaries documented bowel functions for 8 days prior and 8 days during colesevelam treatment. Stool 48-h samples and fasting serum were collected for faecal fat, faecal bile acid and serum C4.

Results: Colesevelam was associated with significantly increased faecal total bile acid excretion and deoxycholic acid excretion, increased serum C4 and more solid stool consistency. There was a significant inverse correlation between number of bowel movements per week and the total bile acid sequestered into stool during the last 48 h of treatment. Random stool samples did not accurately reflect 48-h total or individual faecal bile acid excretion. Sequestration of bile acids by colesevelam did not increase faecal fat.

Conclusions: Colesevelam increases delivery of bile acids to stool while improving stool consistency, and increases hepatic bile acid synthesis, avoiding steatorrhoea in patients with IBS-D. Overall effects are consistent with luminal bile acid sequestration by colesevelam.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allylamine / analogs & derivatives*
  • Allylamine / therapeutic use
  • Bile Acids and Salts / metabolism*
  • Cholestenones / blood
  • Colesevelam Hydrochloride
  • Deoxycholic Acid / metabolism
  • Diarrhea / drug therapy*
  • Feces
  • Female
  • Gastrointestinal Agents / therapeutic use*
  • Humans
  • Irritable Bowel Syndrome / drug therapy*
  • Middle Aged

Substances

  • Bile Acids and Salts
  • Cholestenones
  • Gastrointestinal Agents
  • Deoxycholic Acid
  • 7 alpha-hydroxy-4-cholesten-3-one
  • Allylamine
  • Colesevelam Hydrochloride