Obeticholic acid (OCA) is a selective and potent farnesoid X receptor (FXR) agonist in development for several chronic liver diseases. OCA is a semi-synthetic analogue of chenodeoxycholic acid (CDCA) with similar pharmacokinetic (PK) properties. There was a significant increase in systemic exposure of OCA in patients with hepatic impairment. A proportionally similar increase in systemic exposure of endogenous bile acids was also observed in patients with hepatic impairment.
A physiologic PK model was developed based on a previously reported model for CDCA1 to define the relationship between systemic and hepatic exposure of OCA (and its pharmacologically active conjugates) in patients with and without hepatic impairment (cirrhosis).