Elobixibat hydrate

Elobixibat hydrate (CAS No. 1633824-78-8) is a highly selective inhibitor of the ileal bile acid transporter (IBAT). Its principal pharmacological activity is the inhibition of bile acid reabsorption in the ileal mucosa, thereby modulating the enterohepatic circulation. By increasing colonic bile acid concentrations, elobixibat activates the TGR5 receptor and promotes glucagon-like peptide-1 (GLP-1) secretion, while simultaneously enhancing colonic secretion and motility and improving glucose and lipid metabolism. Clinically, it is primarily indicated for the treatment of chronic idiopathic constipation and may also be used as an adjunct for bowel preparation prior to colonoscopy and for amelioration of metabolic abnormalities associated with type 2 diabetes mellitus (T2DM). Its activity depends on specific blockade of IBAT, with an affinity for the hepatic sodium-dependent bile acid transporter that is more than 450-fold lower.

Commonly used dosing regimens include: oral administration of 10 mg/day in adults for the treatment of chronic constipation; a single 10 mg dose (administered as two 5 mg tablets) taken before breakfast on the day prior to colonoscopy for bowel preparation; and 10 mg/day for 12–24 weeks in patients with T2DM and concomitant constipation. The effective therapeutic concentrations correspond to these clinical oral doses: in patients with chronic constipation, 10 mg once daily significantly increases the number of spontaneous bowel movements per week (by approximately 4.0–5.4 from baseline) and improves stool consistency; in patients with T2DM, 12 weeks of treatment reduces HbA₁c by about 0.2% and lowers LDL-C by 21.4 mg/dL. When used in combination with other laxatives for bowel preparation, elobixibat can achieve adequate cleansing, with a Boston Bowel Preparation Scale (BBPS) score ≥ 6.

After oral administration, elobixibat exhibits low systemic bioavailability, with plasma concentrations in the picomolar range, a protein binding rate exceeding 99%, and a half-life of less than 4 hours. Adverse effects are predominantly mild to moderate and include abdominal pain, abdominal distension, and diarrhea; no serious safety concerns have been identified.

References:

[1] Acosta A, Camilleri M. Elobixibat and its potential role in chronic idiopathic constipation. Therap Adv Gastroenterol. 2014 Jul;7(4):167-75. doi: 10.1177/1756283X14528269. PMID: 25057297; PMCID: PMC4107709.

[2] Yoshinobu S, Hasuzawa N, Nagayama A, Iwata S, Yasuda J, Tokubuchi R, Kabashima M, Gobaru M, Hara K, Murotani K, Moriyama Y, Ashida K, Nomura M. Effects of Elobixibat, an Inhibitor of Ileal Bile Acid Transporter, on Glucose and Lipid Metabolism: A Single-arm Pilot Study in Patients with T2DM. Clin Ther. 2022 Oct;44(10):1418-1426. doi: 10.1016/j.clinthera.2022.08.009. Epub 2022 Sep 16. PMID: 36117045.

[3] Hotta K, Otake Y, Yamaguchi D, Shimodate Y, Hanabata N, Ikematsu H, Yabuuchi Y, Sano Y, Shimoda R, Sugimoto S, Oba M, Takamaru H, Kimura K, Kishida Y, Takada K, Ito S, Imai K, Hosotani K, Murano T, Yamada M, Shinmura K, Takezawa R, Tomonaga M, Saito Y. Comparison of the efficacy and tolerability of elobixibat plus sodium picosulfate with magnesium citrate and split-dose 2-L polyethylene glycol with ascorbic acid for bowel preparation before outpatient colonoscopy: a study protocol for the multicentre, randomised, controlled E-PLUS trial. BMC Gastroenterol. 2024 Feb 3;24(1):61. doi: 10.1186/s12876-024-03146-6. PMID: 38310266; PMCID: PMC10837887.