prucalopride and Gastroesophageal-Reflux

Ineffective esophageal motility (IEM) is associated with gastroesophageal reflux disease. Secondary peristalsis contributes to esophageal clearance. Prucalopride promotes secondary peristalsis by stimulating 5-hydroxytrypatamine 4 receptors in the esophagus. We aimed to determine whether prucalopride would augment secondary peristalsis in gastroesophageal reflux disease patients with IEM.. After a baseline recording of primary peristalsis, secondary peristalsis was stimulated by slow and rapid mid-esophageal injections of air in 15 patients with IEM. Two separate sessions with 4-mg oral prucalopride or placebo were randomly performed.. Prucalopride significantly increased primary peristaltic wave amplitude (68.1 ± 10.0 vs 55.5 ± 8.8 mmHg, P = 0.02). The threshold volume for triggering secondary peristalsis was significantly decreased by prucalopride during slow (9.3 ± 0.8 vs 12.0 ± 0.8 mL; P = 0.04) and rapid air injection (4.9 ± 0.3 vs 7.1 ± 0.1 mL; P = 0.01). Secondary peristalsis was triggered more frequently after application of prucalopride (55% [43-70%]) than placebo (45% [33-50%]) (P = 0.008). Prucalopride did not change pressure wave amplitudes during slow air injection (84.6 ± 8.1 vs 57.4 ± 13.8 mmHg; P = 0.19) or pressure wave amplitudes during rapid air injection (84.2 ± 8.6 vs 69.5 ± 12.9 mmHg; P = 0.09).. Prucalopride enhances primary peristalsis and mechanosensitivity of secondary peristalsis with limited impact on secondary peristaltic activities in IEM patients. Our study suggests that prucalopride appears to be useful in augmenting secondary peristalsis in patients with IEM only via sensory modulation of esophageal secondary peristalsis.

Topics: Adult; Aged; Benzofurans; Esophagus; Female; Gastroesophageal Reflux; Gastrointestinal Motility; Humans; Male; Middle Aged; Peristalsis; Serotonin 5-HT4 Receptor Agonists; Stimulation, Chemical; Treatment Outcome

The 5-HT4 receptor agonist prucalopride is a prokinetic drug which improves colonic motility. Animal data and in vitro studies suggest that prucalopride also affects gastric and esophageal motor function. We aimed to assess the effect of prucalopride on gastric emptying, esophageal motility, and gastro-esophageal reflux in man.. In this double-blind, placebo-controlled, randomized, crossover study, we included 21 healthy volunteers who received 4 mg prucalopride or placebo per day for 6 days. We performed high-resolution manometry (HRM) followed by 120-min HRM-pH-impedance monitoring after a standardized meal, ambulatory 24-h pH-impedance monitoring, and gastric emptying for solids.. Prucalopride decreased (median [IQR]) total acid exposure time (3.4 [2.5-5.6] vs 1.7 [0.8-3.5] %, p < 0.05). The total number of reflux events was unaffected by prucalopride, however, the number of reflux events extending to the proximal esophagus was reduced by prucalopride (15.5 [9.8-25.5] vs 10.5 [5.3-17.5], p < 0.05). Furthermore, prucalopride improved acid clearance time (77.5 [47.8-108.8] vs 44.0 [30.0-67.8] s, p < 0.05). Prucalopride did not affect the number of transient lower esophageal sphincter (LES) relaxations or their association with reflux events. Esophageal motility and basal pressure of the LES were not affected by prucalopride. Prucalopride increased gastric emptying (T1/2 ; 32.7 [27.9-44.6] vs 49.8 [37.7-55.0] min, p < 0.05) and decreased residue after 120 min (8.8 [4.4-14.8] vs 2.7 [1.3-5.4] %, p < 0.05).. Prucalopride reduces esophageal acid exposure and accelerates gastric emptying in healthy male volunteers. These findings suggest that the drug could be effective for treatment of patients with reflux disease and functional dyspepsia.

Topics: Benzofurans; Cross-Over Studies; Double-Blind Method; Gastric Acidity Determination; Gastric Emptying; Gastroesophageal Reflux; Healthy Volunteers; Humans; Hydrogen-Ion Concentration; Male; Manometry; Serotonin 5-HT4 Receptor Agonists