Effects of conventional and a novel colonic-release bile acid sequestrant, A3384, on fibroblast growth factor 19 and bile acid metabolism in healthy volunteers and patients with bile acid diarrhoea

United European Gastroenterology Journal
Richard N ApplebyJrf Walters

Abstract

Primary bile acid diarrhoea (BAD) is associated with increased bile acid synthesis and low fibroblast growth factor 19 (FGF19). Bile acid sequestrants are used as therapy, but are poorly tolerated and may exacerbate FGF19 deficiency. The purpose of this study was to evaluate the pharmacological effects of conventional sequestrants and a colonic-release formulation preparation of colestyramine (A3384) on bile acid metabolism and bowel function in patients with BAD. Patients with seven-day (75)selenium-homocholic acid taurine (SeHCAT) scan retention <10% were randomised in a double-blind protocol to two weeks treatment with twice-daily A3384 250 mg (n = 6), 1 g (n = 7) or placebo (n = 6). Thirteen patients were taking conventional sequestrants at the start of the study. Symptoms were recorded and serum FGF19 and 7α-hydroxy-4-cholesten-3-one (C4) measured. Median serum FGF19 on conventional sequestrant treatment was 28% lower than baseline values in BAD (p < 0.05). C4 on conventional sequestrant treatment was 58% higher in BAD (p < 0.001). No changes were seen on starting or withdrawing A3384. A3384 improved diarrhoeal symptoms, with a median reduction of 2.2 points on a 0-10 Likert scale compared to placebo, p < 0.05. Serum FGF19...Continue Reading

References

May 12, 2009·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Julian R F WaltersCarel W le Roux
Nov 3, 2009·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Suwebatu T Odunsi-ShiyanbadeAlan R Zinsmeister
Jun 6, 2014·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Richard N Appleby, Julian R F Walters
Oct 21, 2014·Alimentary Pharmacology & Therapeutics·J R F WaltersD A Shapiro
Jan 17, 2015·Alimentary Pharmacology & Therapeutics·M CamilleriL J Donato

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Citations

Aug 21, 2018·Endocrine Reviews·Emmanuel Somm, François R Jornayvaz
Feb 23, 2019·United European Gastroenterology Journal·Joost Ph Drenth
Jun 23, 2018·Nature Reviews. Gastroenterology & Hepatology·Magnus Simrén, Jan Tack

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