Duration of anti-cholecystokinin (CCK) action on the rat exocrine pancreas of new CCK receptor antagonist FK 480 administered orally

We assessed the duration of the anti-cholecystokinin (CCK) action of FK480, a new non-peptide CCK-A receptor antagonist developed in Japan, in an in vivo study in rats, comparing it with CR 1505. Pancreatic exocrine secretion stimulated by intravenous infusion of CCK-8 (0.06 μg/kg per h) was measured at intervals of 0–24 h after the oral administration of FK480 (1.5 mg/kg) and CR 1505 (30 mg/kg). FK480 significantly inhibited both CCK-stimulated pancreatic juice volume flow and amylase output 0, 4, 8, and 12h after oral administration, whereas the inhibitory effect of CR 1505 had completely disappeared by 8h after oral administration. It was concluded that orally administered FK480 has a prolonged anti-CCK action.