THE CCK1 ANTAGONIST DEXLOXIGLUMIDE ACCELERATES GASTRIC EMPTYING AND DELAYS EMPTYING OF THE ASCENDING COLON IN CONSTIPATION-PREDOMINANT IRRITABLE BOWEL SYNDROME (C-IBS) PATIENTS: 854

Purpose: Cholecystokinin (CCK) regulates gastrointestinal responses to meals. The effects of CCK1 peripheral receptor antagonists in functional gastrointestinal disorders are unclear. Our aim was to study the effects of the CCK1 receptor antagonist dexloxiglumide on gastrointestinal transit and symptoms in c-IBS. Methods: 36 female patients with C-IBS were randomized to 7 days of dexloxiglumide 200 mg (n = 18) or placebo (n = 18) t.i.d. Daily bowel functions and weekly satisfactory relief of IBS were recorded. At baseline and at the end of treatment, gastrointestinal and colonic transit was measured by scintigraphy using 99mTc-egg meal and 111In- activated charcoal respectively. The relationship between colonic transit and bowel function was evaluated. Results: (Table): Dexloxiglumide accelerated gastric emptying (GE)(p = 0.004) and delayed ascending colon (AC) emptying t1/2 (p <0.01 after adjusting for baseline colonic transit). There was no significant effect on satisfactory relief or bowel function. Changes in aggregate stool scores and stool consistency were associated with colonic transit geometric center (GC) at 24 and 48 hours (p = 0.05 and p <0.01, respectively).TableConclusions: Dexloxiglumide accelerates gastric emptying and retards ascending colon transit in C-IBS. These data suggest dexloxiglumide should be evaluated in functional gut disorders associated with rapid proximal colonic transit or those with delayed gastric emptying.