OPIOID-INDUCED DELAY IN GASTRIC-EMPTYING - A PERIPHERAL MECHANISM IN HUMANS

Background Opioids delay gastric emptying, which in turn may increase the risk of vomiting and pulmonary aspiration. Naloxone reverses this opiate action on gastric emptying, but it is not known whether this ef fect in humans is mediated by central or peripheral opiate antagonism. The importance of peripheral opioid receptor antagonism in modulating opioid-induced delay in gastric emptying was evaluated using methylna ltrexone, a quaternary derivative of the opiate antagonist naltrexone, which does not cross the blood-brain barrier. Methods: In a randomize d, double-blind, crossover placebo-controlled study, 11 healthy volunt eers were given either placebo (saline), 0.09 mg/kg morphine, or 0.09 mg/kg morphine plus 0.3 mg/kg methylnaltrexone on three separate occas ions before ingesting 500 ml deionized water. The rate of gastric empt ying was measured by two methods: a noninvasive epigastric bioimpedanc e technique and the acetaminophen absorption test. Results: The epigas tric bioimpedance technique was sufficiently sensitive to detect opioi d-induced changes in the rate of gastric emptying. The mean +/- SD tim e taken for the gastric volume to decrease to 50% (t(0.5) after placeb o was 5.5 +/- 2.1 min. Morphine prolonged gastric emptying to (t(0.5)) of 21 +/- 9.0 min (P < 0.03). Methylnaltrexone given concomitantly wi th morphine reversed the morphine-induced delay in gastric emptying to a t(0.5) of 7.4 +/- 3.0 (P < 0.04). Maximum concentrations and area u nder the concentration curve from 0 to 90 min of serum acetaminophen c oncentrations after morphine were significantly different from placebo and morphine administered concomitantly with methylnaltrexone (P < 0. 05). No difference in maximum concentration or area under the concentr ation curve from 0 to 90 min was noted between placebo and methylnaltr exone coadministered with morphine. Conclusions: The attenuation of mo rphine-induced delay in gastric emptying by methylnaltrexone suggests that the opioid effect is mediated outside the central nervous system. Methylnaltrexone may have the potential to decrease the side effects of opioid medications, which are mediated peripherally, while maintain ing the central analgesia effect of the opioid.