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

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.