Magnetic Resonance Imaging Reveals Novel Insights into the Dual Mode of Action of Bisacodyl: A Randomized, Placebo-controlled Trial in Constipation

Aliyu, Abdulsalam; Dellschaft, Neele; Hoad, Caroline; Williams, Hannah; Gaudoin, Emily; Sulaiman, Sarah; Crooks, Colin; Gowland, Penny; Aran, Alexia; Lange, Robert; Bois De Fer, Beatrice; Corsetti, Maura; Marciani, Luca; Spiller, Robin

Abstract

Bisacodyl is a widely used laxative that stimulates both motility and secretion. Our aim was to exploit the unique capabilities of MRI to define bisacodyl's mode of action. Two placebo-controlled cross-over trials were performed, one using a single dose of Bisacodyl 5 mg while the second dosed daily for 3 consecutive days. Serial MRI was performed every 75 minutes. Primary endpoint: ascending colon water content as assessed by T1AC AUC300–450 minutes. Secondary endpoints included: small bowel water content, whole gut transit time (WGTT), colonic volumes, stool frequency, and consistency using Bristol Stool Form Score (BSFS). Exploratory endpoints: changes in the serial segmental volumes were quantified from the number of “mass movements” defined as episodes when segmental volume change from the previous scan was > 20% of baseline volume. We also measure the time to defecate after dosing. After 3 days of bisacodyl, ascending colon water content (T1) was 62% greater than after placebo, mean difference T1 AUC300–450 minutes 50.2 (61.0) sec.min, 95% CI (9.2, 91.2), P = 0.02, while after a single dose difference was only 11% (P = 0.58). Both single and repeated doses shortened WGTT (P < 0.049) and time to defecate (P 0.01). Only repeated doses significantly increased small bowel water content (P < 0.03), the number of “mass movements” (P = 0.048), bowel frequency (P = 0.006), and BSFS (P = 0.03). Repeated, compared to single dosing of Bisacodyl, additionally increases small bowel and colon water content and increases the number of “mass movements” thereby increasing its laxative effect. MRI is a non-invasive, patient-acceptable technique for evaluating drugs which alter secretion and/or motility.

Citation

Aliyu, A., Dellschaft, N., Hoad, C., Williams, H., Gaudoin, E., Sulaiman, S., Crooks, C., Gowland, P., Aran, A., Lange, R., Bois De Fer, B., Corsetti, M., Marciani, L., & Spiller, R. (2024). Magnetic Resonance Imaging Reveals Novel Insights into the Dual Mode of Action of Bisacodyl: A Randomized, Placebo-controlled Trial in Constipation. Clinical Pharmacology and Therapeutics, https://doi.org/10.1002/cpt.3532

• Journal Article Type: Article
• Acceptance Date: Dec 2, 2024
• Online Publication Date: Dec 16, 2024
• Publication Date: Dec 16, 2024
• Deposit Date: Dec 13, 2024
• Publicly Available Date: Dec 17, 2024
• Journal: Clinical Pharmacology and Therapeutics
• Print ISSN: 0009-9236
• Electronic ISSN: 1532-6535
• Publisher: American Society for Clinical Pharmacology and Therapeutics
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1002/cpt.3532
• Public URL: https://nottingham-repository.worktribe.com/output/42838571
• Publisher URL: https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.3532
• Additional Information: Received: 2024-09-11; Accepted: 2024-12-02; Published: 2024-12-16