Elobixibat and its potential role in chronic idiopathic constipation

Abstract

Chronic idiopathic constipation is highly prevalent among adults. Bile acids (BAs) and the enterohepatic BA circulation modulate colonic secretion and motility that affect transit. BAs in the colon have a dual action as osmotic and stimulant agents. Newer agents, such as elobixibat (A3309), an inhibitor of the ileal BA transporter, have the potential to improve significantly the management of chronic constipation, with minimal adverse effects. Elobixibat modulates the enterohepatic BA circulation, enhancing the delivery of BAs to the colon where they induce secretory and motor effects. Secondary effects of the inhibition of BA absorption are reduced activation of the farnesoid X receptor, decreased secretion of fibroblast growth factor-19 into the portal circulation, and increased BA synthesis. This review focuses on the role of BAs, the enterohepatic BA circulation, and an ileal BA transporter inhibitor (elobixibat) in chronic constipation.