Effect of EM574 on Postprandial Pancreaticobiliary Secretion, Gastric Motor Activity, and Emptying in Conscious Dogs

EM574, an erythromycin derivative and a potentmotilin receptor agonist, is now under clinical trial asa gastroprokinetic drug. The aim of this study was toestimate the effect of EM574 on postprandial pancreaticobiliary secretion, gastric motoractivity, and emptying in conscious dogs. Five mongreldogs were prepared. Indwelling cannulas for bothinfusion of phenolsulfonphthalein and aspiration ofluminal samples were inserted into the proximal anddistal duodenum, respectively. EM574 (3-30 g/kg) wasgiven intraduodenally through the indwelling distalduodenal cannula at the start of feeding. Postprandial pancreatic and biliary secretions were assessedby measuring the outputs of amylase and bile acid intothe duodenum, respectively. Gastric motor and emptyingactivity were measured by means of a force transducer method and our own freeze-drying method,respectively. One hundred grams of a freeze-driedstandard meal was given as a solid marker after beingmixed with 100 ml of normal saline containing 15 g ofpolyethylene glycol as a liquid marker. EM574 at doses of 10and 30 g/kg significantly increased the meanintegrated postprandial amylase output into theduodenum, but the mean integrated postprandial bile acidoutput was not significantly increased. EM574increased postprandial gastric antral motor activitydosedependently. EM574 at doses of 10 and 30 g/kgsignificantly accelerated gastric emptying of liquidsand solids, respectively. EM574 enhances gastricantral motor activity and accelerates gastric emptyingof solids and liquids with a concomitant increase inpostprandial pancreatic amylase, but not bile acid, output in normal dogs.