Impact of Itopride and Domperidone on sensitivity of gastric distention and gastric accommodation in healthy volunteers. Karen Van den Houte, Florencia Carbone, Ans Pauwels, Rita Vos, Tim Vanuytsel, Jan Tack Translational Research Center for Gastrointestinal Disorders, KULeuven, Belgium
BACKGROUND & AIM RESULTS Functional dyspepsia (FD), defined as upper abdominal symptoms affecting Conduct of the study Gastric accommodation daily life, as postprandial fullness, early satiation, epigastric pain, and epigastric • 15 healthy volunteers (9 female, 6 male) • No significant differences in VAS scores before and after meal burning, without any underlying organic disease, is one of the most common • Mean age: 28.3±5.8 years ingestion and no significant differences in preprandial intragastric functional gastrointestinal disorders (1). volumes were observed. Itopride, a prokinetic drug with dopamine D2-antagonistic and cholinesterase Gastric compliance and gastric sensitivity • Postprandial gastric volumes and gastric accommodation were inhibitor properties, is frequently used to treat functional dyspepsia. Its effects I50, I100, and D10 did not affect fasting or postprandial gastric significantly lower for I50 and for D10, compared to placebo. on gastric sensitivity and accommodation are unknown (2), compliance and gastric sensitivity to distention significantly The aim of this study is to evaluate the effect of Itopride, compared to compared to placebo. Domperidone, a dopamine D2 receptor antagonist, on the sensitivity to gastric * Placebo balloon distention and on meal-induced relaxation of the stomach. 500 ** 800 800 I100 Placebo I100 I50 D10 Placebo I100 I50 D10 700 700 450 I50 METHODS 600 600 400 D10 500 • Placebo-controlled, double-blind cross-over design 500 400 400 350
300 300 Volume (ml) Volume • Gastric barostat study (ml) Volume 300 200 200 ** • Pre-treatment for two days three times daily: 100 100 250 *** 0 0
Placebo (P) Polyethylene bag 2 4 6 8 2 4 6 8 200 balloon(ml) volume Itopride 50mg (I50) Pressures from MDP (mmHg) in the preprandial state Pressures from MDP (mmHg) in the postprandial state - 150
Itopride 100mg (I100) Intra Domperidone 10mg (D10) 100 50
5 5 0 • Determination of gastric compliance as the slope of the pressure/volume Placebo I100 I50 D10 Placebo I100 I50 D10 Preprandial Postprandial Accommodation curve during stepwise distentions. 4 4
• Determination of gastric sensitivity: 3 3
a) as the slope of the pressure/perception score during stepwise distentions 2 2 TAKE HOME MESSAGE Perception score Perception b) as the threshold pressure inducing first perception and discomfort score Perception 1 1 Scored by visual analogue scales (VAS) 0 0 • Gastric accommodation was quantified by subtracting mean preprandial 2 4 6 8 2 4 6 8 Pressures from MDP (mmHg) in the preprandial state Pressures from MDP (mmHg) in the postprandial state I50, I100, and D10 do not affect gastric compliance 35 minutes volumes from mean postprandial 60 minutes volumes. and sensitivity to distention compared to placebo.
Fasting treshold Fasting discomfort Meal-related gastric accommodation was reduced Pressure (mmHg) Volume (ml) Pressure (mmHg) Volume (ml) by I50 and D10, but preserved by I100.
Preprandial Postprandial Preprandial Postprandial Preprandial Postprandial Preprandial Postprandial
Placebo 8.7±1.16 9.7±1.26 192.6±36.63 512.7±60.12 17.3±1.22 15.3±1.37 666.2±48.08 779.9±58.22
I100 8.4±1.19 8.4±1.28 220.1±38.94 409.6±53.45 16.6±1.59 15.4±1.61 656.7±71.92 772.1±49.60 References I50 7.7±1.03 8.1±1.14 191.8±29.48 423.1±47.13 16.2±1.24 15.1±1.37 627.2±49.39 763.8±46.62 (1) Mahadeva S, Goh KL. Epidemiology of functional dyspepsia: a global perspective. World J Gastroenterol. 2006;12(17):2661-6. (2) Holtmann G, Talley NJ, Liebregts T, Adam B, Parow C. A placebo-controlled trial of itopride in functional dyspepsia. D10 8.0±1.20 7.7±1.21 205.2±34.92 368.4±46.30 16.0±1.33 14.5±1.23 677.2±48.86 772.1±49.09 N Engl J Med. 2006;354(8):832-40.
Van den Houte Karen| [email protected]