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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.


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 75selenium-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 7?-hydroxy-4-cholesten-3-one (C4) measured.Median serum FGF19 on conventional sequestrant treatment was 28% lower than baseline values in BAD (p?

SUBMITTER: Appleby RN 

PROVIDER: S-EPMC5415210 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

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