THE EFFECT OF METOCLOPRAMIDE, ONDANSETRON, AND GRANISETRON ON LIQUID GASTRIC-EMPTYING IN NORMAL SUBJECTS

The present study, carried out in nine healthy male volunteers, invest igated the effects of metoclopramide, ondansetron, and granisetron on gastric emptying of liquids, as assessed by the percentage cumulative fraction absorbed-time profiles of paracetamol. A single-blind, crosso ver, randomized design was followed that allowed at least a 2-week int erval between study sessions. On each occasion, 1.5 g paracetamol was taken at zero time (6 AM). One of the following treatments was adminis tered intravenously on four occasions at -30 minutes (5:30 AM): 8 mg o ndansetron; 3 mg granisetron in 20 mL saline; 20 mg metoclopramide, by slow injection over 5 minutes; or 10 mL saline as placebo. The percen tage cumulative fraction absorbed-time profiles of paracetamol were ca lculated from serial serum paracetamol concentration measurements usin g the Wagner-Nelson method. With granisetron pretreatment, significant ly lower cumulative fractions of paracetamol were absorbed than after saline pretreatment at 120 minutes. The results suggest that in humans , granisetron-without additional pharmacologic effects-may retard gast ric emptying, as it appears to be a more selective 5-hydroxytryptamine (3) antagonist than ondansetron or metoclopramide.