492 Influence of Itopride On Esophageal Function in Man

Abstract

Introduction: Defective barrier function of the lower esophageal sphincter (LES), caused by a hypotonic sphincter or transient lower esophageal sphincter relaxations (TLESRs), is a major factor in the pathogenesis of gastroesophageal reflux disease (GERD). Itopride is a new prokinetic agent which combines antidopaminergic and acetylcholinesterase inhibitory actions. Previous studies suggested that itopride improves heartburn in functional dyspepsia patients, and decreases esophageal acid exposure in GERD. It is unclear whether this effect is due to motor effects of itopride on the LES. Aims: To study the effects of itopride on fasting and postprandial LES function in healthy subjects. Materials and methods: twelve fasted healthy volunteers (5 males; 32.6±2.0 years) underwent three esophageal sleeve manometry studies after 3 days premedication with itopride 50 mg, itopride 100 mg or placebo t.i.d. Drug was administered after 30 minutes and a standardized meal was administered after 90 minutes, with measurements continuing to 120 minutes postprandially. Throughout the study, 10 wet swallows were administered at 30-minute intervals, and gastrointestinal symptoms were scored on 100 mm visual analogue scales (VAS) at 10minute intervals. Results: Both doses of itopride significantly decreased intragastric pressures compared to placebo (respectively 16.0±1.3 and 17.3±1.5 vs. 20.4±1.7mmHg, both p<0.05). Compared to placebo, the 50 mg dose of itopride was associated with a lower LES pressure before the meal (17.3±3.0 vs. 11.8±1.6 mmHg, p<0.05), but postprandial LES pressures did not differ from placebo for any time points for both doses of itopride. Swallow-induced relaxations and the amplitude or duration of peristaltic contractions were not altered by both doses of itopride, at all time points. The 50 mg dose of itopride inhibited TLESRS compared to placebo (TLESRs total 1.7±0.7 vs. 3.3±0.5, p=0.03; preprandially 0.4±0.3 vs.1.3±0.3, p=0.04; postprandially 1.3±0.4 vs. 2.0±0.4, p=0.16). The 100 mg dose did not significantly alter the rate of TLESRs before or after the meal. Conclusions: Itopride 50 mg inhibits TLESRswithout significantly affecting esophageal peristaltic function or LES pressure. Both doses of itopride decrease intragastric pressures. Identifying the nature and location of the receptors involved in this effect of itopride requires additional studies. Our observations support further studies with itopride in GERD.