Comparative potency of obeticholic acid and natural bile acids on FXR in hepatic and intestinal in vitro cell models.

ABSTRACT: Obeticholic acid (OCA) is a semisynthetic farnesoid X receptor (FXR) agonist, an analogue of chenodeoxycholic acid (CDCA) which is indicated for the treatment of primary biliary cholangitis (PBC) in combination with ursodeoxycholic acid (UDCA). OCA efficiently inhibits bile acid synthesis and promotes bile acid efflux via activating FXR-mediated mechanisms in a physiologically relevant in vitro cell system, Sandwich-cultured Transporter Certified ™ human primary hepatocytes (SCHH). The study herein evaluated the effects of UDCA alone or in combination with OCA in SCHH. UDCA (≤100 μmol/L) alone did not inhibit CYP7A1 mRNA, and thus, no reduction in the endogenous bile acid pool observed. UDCA ≤100 μmol/L concomitantly administered with 0.1 μmol/L OCA had no effect on bile acid synthesis bey

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC5723701 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature