EFFECT OF LINTITRIPT, A NEW CCK-A RECEPTOR ANTAGONIST, ON GASTRIC-EMPTYING OF A SOLID-LIQUID MEAL IN HUMANS

The role of cholecystokinin (CCK) in the regulation of gastric emptyin g of physiological meals containing solids and liquids in humans remai ns controversial. We studied the role of endogenous CCK in the emptyin g of a solid/liquid meal administering the new, highly specific and po tent CCK-A receptor antagonist lintitript. Gastric emptying was assess ed in nine healthy male volunteers using a randomized, double blind, t wo-period crossover design with oral lintitript (15 mg 1 h prior to me al intake) or placebo on two different days. After ingestion of a panc ake (570 kcal) labelled with 500 mu Ci of Tc-99m-sulfur colloid and 50 0 ml 10% dextrose containing 80 mu Ci In-111-DTPA, subjects were studi ed in a sitting position, using a dual-headed gamma camera. Plasma CCK and pancreatic polypeptide (PP) were measured by a specific RIA. Lint itript distinctly accelerated gastric emptying of solids, while gastri c emptying of liquids was not significantly altered. The lag period wa s shortened by 20% (P < 0.05), AUC and half emptying time of solid emp tying were lowered by 12% and 13%, respectively (P < 0.03). Lintitript markedly increased postprandial plasma CCK release (P < 0.001) while distinctly reducing postprandial PP levels (P < 0.01) as compared to p lacebo. These data provide further evidence for a significant role of CCK in the regulation of gastric emptying of solids. The study demonst rates for the first time the marked gastrokinetic properties of the ne w CCK-A receptor antagonist lintitript in humans. (C) 1998 Elsevier Sc ience B.V.