Effects of A3309, an ileal bile acid transporter inhibitor, on colonic transit and symptoms in females with functional constipation
Abstract
OBJECTIVES: Delivery of bile acid (BA) to the colon stimulates propulsive motility and fluid secretion. The objective of this study was to examine gastrointestinal (GI) transit effects of A3309, a small molecule inhibitor of the ileal BA transporter, in patients with functional constipation (FC). METHODS: In a double-blind, placebo-controlled study of 36 female FC patients randomized to placebo, 15 mg A3309, or 20 mg A3309 administered orally once daily for 14 consecutive days, we assessed GI and colonic transit, stool characteristics, symptoms of constipation, fasting serum C4 (7α-hydroxy-4-cholesten-3-one) (surrogate of BA synthesis and malabsorption), and fasting serum total and low-density lipoprotein (LDL) cholesterol (surrogates of inhibition of BA absorption). Following the intention-to-treat paradigm, we used analysis of covariance to assess the overall treatment effects and Dunnett's test for pairwise comparisons. RESULTS: Overall colonic transit (geometric center at 24 h) was significantly accelerated with 20 mg A3309 compared with placebo (overall effect, P=0.059; A3309 15 mg, P=0.18; and A3309 20 mg, P=0.04). Colonic transit at 48 h was significantly accelerated with both A3309 dosages (overall effect, P<0.001; A3309 15 mg, P=0.002; and A3309 20 mg, P<0.001). Significantly looser stool consistency was noted with both A3309 dosages compared with placebo (P<0.005). Significant effects of A3309 on constipation rating, ease of stool passage, and reduction of straining were also detected. The most common side effect was lower abdominal cramping/pain. A3309 treatment significantly and reversibly increased fasting C4 (A3309 15 mg, P=0.05; A3309 20 mg, P<0.01) but did not affect fasting total and LDL cholesterol. CONCLUSIONS: A3309 accelerates colonic transit and loosens stool consistency in FC patients.
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Inhibition of the ileal bile acid transporter by elobixibat accelerated colonic transit in patients with constipation.
“Inhibition of the ileal bile acid transporter by elobixibat accelerated colonic transit in patients with constipation”
From Irritable bowel syndrome (2020) · cites this paper as [141]
Studies on functional constipation patients treated with the ileal bile acid transporter inhibitor elobixibat demonstrated a causal relationship between elevated bile acid level and improved colonic transit.
“Several studies on FC patients treated with an ileal BA transporter inhibitor (elobixibat) demonstrated a causal relationship between elevated BA level and improved colonic transit [ 40–43 ].”
From Role of gut microbiota in functional constipation (2021) · cites this paper as [41]
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Review article: Elobixibat: a novel treatment for chronic constipation
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Current and Emerging Pharmacotherapeutic Options for Irritable Bowel Syndrome
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Bile Acid Diarrhea and NAFLD: Shared Pathways for Distinct Phenotypes
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- Authors
- Wong, B. S., Camilleri, M., McKinzie, S., Burton, D., Graffner, H., & Zinsmeister, A. R.
- Affiliations
- Mayo Clinic (US)
- Albireo (Sweden) (SE)
- Corresponding author
- Camilleri, Michael
- Venue
- American Journal of Gastroenterology
- Published
- 2011-12
- Volume
- 106
- Issue
- 12
- Pages
- 2154-2164
- ISSN
- 0002-9270 (ISSN-L)
- OpenAlex
- W2038085292
- Cited by
- 133
- References
- 39
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 2 · 2023: 7 · 2022: 8 · 2021: 6 · 2020: 9 · 2019: 6 · 2018: 15 · 2017: 13 · 2016: 11 · 2015: 16 · 2014: 12 · 2013: 6 · 2012: 9
- FWCI
- 9.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Rheumatology › Pelvic floor disorders treatments
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- ileal bile acid transporter inhibitors, functional constipation, colonic transit, bile acid malabsorption, stool consistency, constipation symptoms, cholesterol, female patients, gastrointestinal motility, straining, abdominal cramping, drug safety and tolerability, bile acid sequestrants
- MeSH terms
- Adult, Carrier Proteins, Cholestenones, Colic, Colon, Constipation, Diarrhea, Double-Blind Method, Feces, Female, Gastric Emptying, Gastrointestinal Transit, Humans, Lipoproteins, LDL, Membrane Glycoproteins, Middle Aged, Treatment Outcome, Symporters, Organic Anion Transporters, Sodium-Dependent
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