Tenapanor hydrochloride for the treatment of constipation-predominant irritable bowel syndrome

Abstract

Introduction: Constipation-predominant irritable bowel syndrome (IBS-C) is a common functional gastrointestinal (GI) disorder characterized by recurrent abdominal pain and prolonged GI transit. The pathogenesis of IBS-C has still not been established; therefore, drugs currently in use in IBS-C act mainly symptomatically, whereas novel pharmacological targets are urgently needed. Tenapanor is a potent inhibitor of Na⁺/H⁺ exchanger 3 [NHE3], localized in the apical membrane of intestinal epithelial cells. NHE3 participates in the uptake of sodium ions and water from the intestinal lumen.

Areas covered: In this review, the authors discuss pharmacodynamics and pharmacokinetics of tenapanor, focusing on animal models and in vitro studies. They also summarize clinical trials on tenapanor’s safety and efficacy in view of its potential role in IBS-C therapy.

Expert opinion: Tenapanor possesses an excellent preclinical safety profile and, as of now, there are no serious concerns about its side effects. The non-systemic action of tenapanor constitutes a significant advantage, as it minimizes possible adverse effects or drug–drug interactions. However, Phase III clinical trials are still needed to confirm results obtained in earlier phases and optimize the dose–response for tenapanor, whereas limiting diarrhea, its major adverse effect.

Keywords:

• abdominal pain
• constipation
• gastrointestinal motility
• irritable bowel syndrome
• NHE3 inhibitor
• tenapanor

Declaration of interest

The authors are supported by the Iuventus Plus program of the Polish Ministry of Science and Higher Education (0107/IP1/2013/72 awarded to J Fichna), grants from the Medical University of Lodz (#503/1-156-04/503-01 awarded to J Fichna and 502-03/1-156-02/502-14-141 to M Zielińska) and grants from National Science Centre (UMO-2013/11/B/NZ7/01301 and UMO-2014/13/B/NZ4/01179 awarded to J Fichna, UMO-2013/11/N/NZ7/00724 and UMO-2014/12/T/NZ7/00252 to M Zielińska). M Zielińska is the recipient of the Polish L’Oréal UNESCO Awards for Women in Science and Polpharma Scientific Foundation scholarship. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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