Elobixibat, an ileal bile acid transporter inhibitor, induces giant migrating contractions during natural defecation in conscious dogs.

Abstract

Chronic constipation affects 14%-17% of the population. Elobixibat, a novel, ileal bile acid transporter (IBAT) inhibitor, has been approved as a new chronic constipation drug in Japan in January 2018. The present study aimed to examine the pharmacological effects of elobixibat on colonic motility in conscious dogs using a telemetry system. Six male beagle dogs were surgically implanted with strain gauge force transducers for gastrointestinal (GI) motility recording. The motility index was calculated from GI motility at each recording site in conscious and nonrestraint dogs. The fasted dogs were orally administered elobixibat (3, 10, or 30mg kg-1 ) or 30mg kg-1 of sennoside as positive control or vehicle using a crossover design and washout period of more than 6days. One hour after drug administration, the dogs were fed chow, and GI motility and defecation were observed for 10hours; GI motility was quantified to calculate giant migrating contractions (GMCs). Fecal bile acids (BAs) were determined as well. Elobixibat and sennoside significantly increased the number of defecations, fecal wet weight, and water content within 10hours after administration. Elobixibat dose-dependently decreased the time to first bowel movement, increased the amount of total fecal BAs, and rapidly induced mild GMCs during defecation; however, higher strength of GMCs was observed with sennoside. Elobixibat induces bowel movements faster than sennoside through a different mechanism. Elobixibat locally inhibits IBAT in the ileal lumen, leading to elevated fecal BAs in the colon and induced mild GMCs during defecation.