title: Effect of colesevelam on faecal bile acids and bowel functions in diarrhoea-predominant irritable bowel syndrome.
abstract: BACKGROUND
  About one-third of patients with IBS-diarrhoea (irritable bowel syndrome-D) have evidence of increased bile acid synthesis or excretion.
  
  
  OBJECTIVE
  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.
authors.affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA.
authors.forename: M
authors.initials: M
authors.lastname: Camilleri
authors.forename: A
authors.initials: A
authors.lastname: Acosta
authors.forename: I
authors.initials: I
authors.lastname: Busciglio
authors.forename: A
authors.initials: A
authors.lastname: Boldingh
authors.forename: R B
authors.initials: RB
authors.lastname: Dyer
authors.forename: A R
authors.initials: AR
authors.lastname: Zinsmeister
authors.forename: A
authors.initials: A
authors.lastname: Lueke
authors.forename: A
authors.initials: A
authors.lastname: Gray
authors.forename: L J
authors.initials: LJ
authors.lastname: Donato
mesh_terms: D000328:Adult; D000499:Allylamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000378:metabolism*; D002783:Cholestenones / Q000097:blood; D000069472:Colesevelam Hydrochloride; D003840:Deoxycholic Acid / Q000378:metabolism; D003967:Diarrhea / Q000188:drug therapy*; D005243:Feces; D005260:Female; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy*; D008875:Middle Aged
chemical_list: D001647:Bile Acids and Salts; D002783:Cholestenones; D005765:Gastrointestinal Agents; D003840:Deoxycholic Acid; C002656:7 alpha-hydroxy-4-cholesten-3-one; D000499:Allylamine; D000069472:Colesevelam Hydrochloride