High‐resolution manometry reveals different effect of polyethylene glycol, bisacodyl, and prucalopride on colonic motility in healthy subjects: An acute, open label, randomized, crossover, reader‐blinded study with potential clinical implications

Abstract

Background: Polyethylene glycol (PEG), bisacodyl, and prucalopride have been reported to be more effective than placebo in treating patients with constipation but about 50% of the patients still do not respond to these medications. Only bisacodyl and prucalopride are expected to directly stimulate the colonic motility in humans in vivo. As no previous study has done this, the aim of the study was to investigate the effect of PEG, bisacodyl, and prucalopride as compared to placebo on colonic motility assessed by means of the high-resolution manometry (HRM) in healthy subjects.Methods: Ten healthy subjects have been enrolled in an acute, open label, randomized, reader-blinded, crossover study and requested to undergo a colonoscopyassisted HRM measuring their colonic motility before and after oral administration of 13.8 g (two doses) PEG, 10 mg bisacodyl, 2 mg prucalopride, and placebo. Key Results:In the human prepared colon, oral administration of PEG significantly increases the number of low-amplitude long distance propagating contractions (p = 0.007 vs placebo) while bisacodyl significantly increases the number of highamplitude propagating contractions (HAPCs) (all p < 0.01 vs PEG, prucalopride, and placebo). Prucalopride has no major effect on the number of propagating contractions but increases HAPCs amplitude (p = 0.01). Conclusions & Inferences:In humans, PEG, prucalopride, and bisacodyl have distinct effects on colonic motility. This information has clinical implication, as it indicates that the combination of prucalopride and bisacodyl, normally not considered in clinical practice, could be effective in treating patients with constipation refractory to single medications.

Bisacodyl: A review of pharmacology and clinical evidence to guide use in clinical practice in patients with constipation

“…Corsetti, et al 54 Healthy volunteers Bisacodyl (10 mg, oral), PEG (13.8 g), and prucalopride (2 mg) showed distinct effects on colonic phasic activity, with bisacodyl inducing increased numbers of HAPCs compared with PEG and prucalopride…”

“…13,14,68,69 It is currently unclear whether the stimulation of these Recent observations on the different effects on colon motility of some of the currently available constipation treatments (bisacodyl, PEG, and prucalopride) may provide useful information for clinical practice. 54 It is indeed possible that the use of a combination of different medications, which target different colonic motor patterns, could help patients currently not responding to monotherapy. It is also interesting to note that bisacodyl has been used as a rescue medication in many recent clinical trials designed to investigate the efficacy of newer compounds, such as linaclotide and prucalopride.…”

“…The authors found that bisacodyl 5 mg accelerated the emptying of the ascending colon compared with placebo, with a median time of 6.5 hours and 11.0 hours, respectively 53 . More recently, Corsetti et al assessed colonic motility with oral PEG 13.8 g, bisacodyl 10 mg, prucalopride 2 mg, and placebo in 10 healthy volunteers using high‐resolution manometry 54 . Administration of PEG resulted in a significant increase in the number of long‐distance low‐amplitude propagating contractions vs. placebo, whereas bisacodyl significantly increased the number of HAPCs versus PEG, prucalopride, and placebo.…”

“…Administration of PEG resulted in a significant increase in the number of long‐distance low‐amplitude propagating contractions vs. placebo, whereas bisacodyl significantly increased the number of HAPCs versus PEG, prucalopride, and placebo. Prucalopride increased the amplitude of HAPCs and appeared to increase the number of simultaneous pressure increases 54 . Similarly, there have only been a few mechanistic studies investigating the effect of bisacodyl suppositories.…”

Recent Advances in the Management of Severe Gastrointestinal Dysmotility

“… 10 However, supporting the results from the recent international survey, there is now an increasing evidence-base for the 5HT4 agonist Prucalopride in gastrointestinal motility disorders as a pan-gut prokinetic. In addition to its known effects on small bowel and colonic transit, 46 , 47 Prucalopride has recently been shown to improve foregut sensorimotor function, 48–50 and has also previously been shown to have some benefit in improving symptoms in patients with CIPO. 51 The other group of treatments that were reported to be highly effective in the recent survey was neuropathic analgesics.…”