Elobixibat for the treatment of constipation

Victor Chedid, Priya Vijayvargiya, Michael Camilleri

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Introduction: Chronic idiopathic constipation (CC) is highly prevalent worldwide. A subset of patients with CC have reduced fecal (and by inference, intra-colonic) bile acids (BA). Elobixibat, a locally-acting ileal bile acid transporter (IBAT) inhibitor, leads to increased BA delivery to the colon and represents a new class of treatment for CC. BAs accelerate colonic transit and increase colonic secretion. Therefore, IBAT inhibitors have potential to treat patients with CC. Areas covered: Rationale for IBAT inhibitor in therapeutics, and preclinical and clinical pharmacology of elobixibat: In vitro, elobixibat is a highly potent, selective IBAT inhibitor. In humans, elobixibat accelerated colonic transit. In phase 2A, 2B and 3 studies in CC, elobixibat was efficacious, well tolerated and safe. An open-label, phase 3 trial (52 weeks) confirmed the safety of elobixibat. Elobixibat reduces LDL cholesterol, increases serum GLP-1, and has potential in metabolic syndrome. Expert commentary: Uniquely among current treatments of CC, elobixibat stimulates both motor and secretory functions in the colon. These dual effects suggest that, when approved, elobixibat may be a first-line choice for constipation associated with colonic BA deficiency and a second-line treatment for all patients with CC and constipation-predominant irritable bowel syndrome. Further studies are required to confirm efficacy for relief of CC. Once approved, elobixibat will likely become a second-line choice for treatment of CC.

Original languageEnglish (US)
JournalExpert Review of Gastroenterology and Hepatology
DOIs
StateAccepted/In press - Jan 1 2018

    Fingerprint

Keywords

  • Bile acid
  • enterohepatic circulation
  • ileal bile acid transporter (IBAT)
  • irritable bowel syndrome
  • pharmacodynamics
  • pharmacokinetics

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this