摘要：The aim of this study was to investigate the effect of grapefruit juice intake on the antinociception of morphine in rats. The antinociception of morphine (30 mg/kg, per os ( p.o. )) was significantly enhanced by the oral administration of grapefruit juice (2 ml/rat). Further, the effect of grapefruit juice was examined in morphine-tolerant rats. The repeated administration of morphine (100 mg/kg p.o. ) for 5 d caused a marked decrease in the antinociception, indicating the development of morphine-tolerance. In the morphine-tolerant rats, oral administration of grapefruit juice potentiated significantly the antinociceptive effect of morphine. To examine the pharmacokinetics of morphine after the repeated treatment with morphine for 5 d, microdialysis probes were implanted into the jugular vein and spinal intrathecal space in rats. The morphine concentrations in the blood and intrathecal cerebrospinal fluid (CSF) were gradually decreased by the repeated treatment with morphine. The grapefruit juice treatment significantly increased the blood concentration of morphine in morphine-tolerant rats. These results suggest that oral administration of grapefruit juice enhances the morphine antinociception by increasing the intestinal absorption of this agent.
