An FXR Agonist Reduces Bile Acid Synthesis Independently of Increases in FGF19 in Healthy Volunteers

Bile acid (BA) synthesis is regulated through suppression of hepatic cholesterol 7α-hydroxylase via FXR activation in hepatocytes and/or enterocytes; in enterocytes, this process requires FGF19 signaling. To study these pathways, we quantified markers of BA synthesis (7α-hydroxy-4-cholesten-3-one;C4) and cholesterol production (lathosterol), FGF19, and BAs in serum from healthy male volunteers given 1 oral dose of the nonsteroidal FXR agonist Px-102 (0.15mg/kg, 0.3mg/kg, 0.6mg/kg, 1.12mg/kg, 2.25mg/kg, 3.38mg/kg, or 4.5mg/kg).