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

• Background: 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. Aim: 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. Methods: 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 250mg (n=6), 1g (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 alpha-hydroxy-4-cholesten-3-one (C4) measured. Results: 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. Conclusions: Serum FGF19 was suppressed and bile acid production up-regulated on conventional bile acid sequestrants, but not with A3384. This colonic-release formulation of colestyramine produced symptomatic benefit in patients with BAD.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Gastroenterologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Gastroenterology and Hepatology (hsv//eng)

Nyckelord

Bile acid sequestrants

colestyramine

fibroblast growth factor 19

bile acid malabsorption

bile acid

irritable-bowel-syndrome

diurnal-variation

malabsorption

cholestyramine

colesevelam

prevalence

Gastroenterology & Hepatology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)