Elobixibat for the treatment of constipation

Expert Opin Investig Drugs. 2013 Feb;22(2):277-84. doi: 10.1517/13543784.2013.753056. Epub 2012 Dec 8.

Abstract

Introduction: Elobixibat (formerly A3309) is a first-in-class ileal bile acid transporter (IBAT) inhibitor for treatment of chronic idiopathic constipation (CIC; syn functional constipation). CIC affects up to 25% of the general population; and up to a half are unsatisfied with current therapies. There is an unmet need for safe and effective drugs to treat CIC.

Areas covered: The authors present: i) an overview of Phase II clinical trials of elobixibat in CIC, based on peer-reviewed literature and congress presentations and ii) an evaluation of the efficacy and mechanism of action of elobixibat in the treatment of CIC.

Expert opinion: Elobixibat provides a novel approach to treat chronic constipation via IBAT inhibition with enhanced delivery of bile acids to the colon. Pharmacodynamic studies show that it accelerates colonic transit, increases stool frequency, loosens stool consistency and relieves constipation-related symptoms in CIC patients. These beneficial effects are maintained for a minimum of 8 consecutive weeks of treatment. With minimal absorption and low systemic bioavailability, elobixibat is generally well tolerated and may offer the added benefit of improving serum lipid profiles through bile acid depletion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Oral
  • Animals
  • Carrier Proteins / antagonists & inhibitors*
  • Clinical Trials, Phase II as Topic
  • Constipation / drug therapy*
  • Constipation / metabolism
  • Constipation / physiopathology
  • Dipeptides / administration & dosage
  • Dipeptides / adverse effects
  • Dipeptides / pharmacokinetics
  • Dipeptides / therapeutic use*
  • Gastrointestinal Transit / drug effects*
  • Humans
  • Membrane Glycoproteins / antagonists & inhibitors*
  • Molecular Structure
  • Thiazepines / administration & dosage
  • Thiazepines / adverse effects
  • Thiazepines / pharmacokinetics
  • Thiazepines / therapeutic use*
  • Treatment Outcome

Substances

  • Carrier Proteins
  • Dipeptides
  • Membrane Glycoproteins
  • Thiazepines
  • bile acid binding proteins
  • elobixibat