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

EM574, an erythromycin derivative and a potent motilin receptor agonist, is now under clinical trial as a gastroprokinetic drug. The aim of this study was to estimate the effect of EM574 on postprandial pancreaticobiliary secretion, gastric motor activity, and emptying in conscious dogs. Five mongrel dogs were prepared. Indwelling cannulas for both infusion of phenolsulfonphthalein and aspiration of luminal samples were inserted into the proximal and distal duodenum, respectively. EM574 (3-30 microg/kg) was given intraduodenally through the indwelling distal duodenal cannula at the start of feeding. Postprandial pancreatic and biliary secretions were assessed by measuring the outputs of amylase and bile acid into the duodenum, respectively. Gastric motor and emptying activity were measured by means of a force transducer method and our own freeze-drying method, respectively. One hundred grams of a freeze-dried standard meal was given as a solid marker after being mixed with 100 ml of normal saline containing 15 g of polyethylene glycol as a liquid marker. EM574 at doses of 10 and 30 microg/kg significantly increased the mean integrated postprandial amylase output into the duodenum, but the mean integrated postprandial bile acid output was not significantly increased. EM574 increased postprandial gastric antral motor activity dose-dependently. EM574 at doses of 10 and 30 microg/kg significantly accelerated gastric emptying of liquids and solids, respectively. EM574 enhances gastric antral motor activity and accelerates gastric emptying of solids and liquids with a concomitant increase in postprandial pancreatic amylase, but not bile acid, output in normal dogs.