Physician’s Weekly recently spoke with William D. Chey, MD, FACG, AGAF, FACP, RFF, lead author of the phase 3 T3MPO-2 study—which assessed the efficacy of the NHE3 inhibitor tenapanor in treating patients with irritable bowel syndrome with constipation (IBS-C)—about NHE3 inhibitors and their unique method of action (MOA) in treating patients with IBS-C.
PW: How do NHE3 inhibitors work?
Dr. Chey: They block reabsorption of sodium from the small intestine. This leads to passive movement of water and chloride into the gut lumen which offers benefits to constipation by softening the consistency of stool, increasing biomass and secondarily stimulating peristalsis.
How does that MOA differ from that of other treatments for IBS-C?
Lubiprostone, linaclotide, and plecanitide all stimulate chloride and fluid secretion via different chloride channels; They stimulate chloride secretion. NHE3 inhibitors inhibit sodium absorption.
What makes NHE3s particularly useful in treating IBS-C, considering the condition’s multifactorial pathophysiology?
They improve bowel symptoms (stool frequency and consistency) and abdominal symptoms (pain and bloating).
What evidence is there to support the use of NHE3 inhibitors in treating IBS-C?
The phase 2 and 3 randomized controlled trials—T3MPO-1 and T3MPO-2, respectively—published by my colleagues and me in the American Journal of Gastroenterology.
