Review Article

Elobixibat: A Novel Treatment for Chronic Constipation

Lehar Khanna; Michael Camilleri

Disclosures

Aliment Pharmacol Ther. 2021;53(2):234-242. 

In This Article

Abstract and Introduction

Abstract

Background: A subset of patients with chronic constipation has associated slow colonic transit and reduced faecal bile acid excretion. In addition to traditional approaches to treat chronic constipation, a novel therapeutic option is to increase the colonic concentration of intraluminal bile acids. This can be achieved through inhibition of the ileal bile acid transporter.

Aim: To evaluate the evidence for efficacy and safety of an ileal bile acid transport inhibitor in the treatment of chronic constipation

Methods: We reviewed published literature on elobixibat, based on a PubMed search.

Results: Elobixibat is a novel ileal bile acid transport inhibitor that has demonstrated efficacy in proof of concept studies in experimental animals as well as phase 1, 2 and 3 trials in humans. Phase 4 studies have now documented that the beneficial effects are related to increase in the secretory bile acids in the colon as measured by stool bile acid content. The studies documented efficacy in patients with severe constipation, which is often associated with slow colonic transit. These changes in bile acid composition were associated with minor differences in the faecal microbiota in patients treated with elobixibat compared to placebo. Elobixibat appears to be safe. The only adverse effects of note are associated with its pharmacological actions in patients with chronic constipation, namely the induction of diarrhoea and abdominal pain.

Conclusion: This new class of compound appears to be safe and efficacious in the treatment of chronic constipation.

Introduction

Chronic constipation is one of the most common chronic gastrointestinal disorders, with a prevalence of 20% in the general population and with higher incidence in women and elderly.[1] Constipation is associated with excessive straining, hard stools, bloating, sensation of incomplete evacuation and use of manual manoeuvres to facilitate defecation, which negatively affect the quality of life and impose socioeconomic and healthcare burdens.[2] In a survey of 557 participants, 47% were not satisfied with the treatment for constipation.[3] Current therapies for constipation include fibre supplements, stool softeners, osmotic laxatives, prokinetics and secretagogues, with variable efficacy.[4] Hence, there is an unmet need for treatment modalities for chronic constipation. Elobixibat is the world's first bile acid transport inhibitor. It was approved for clinical use in Japan in 2018. We evaluated the published literature on elobixibat, based on a PubMed search using the following search terms: bile acid, enterohepatic circulation, ileal bile acid transporter, irritable bowel syndrome, pharmacodynamics, pharmacokinetics.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....