title: Enhancement by grapefruit juice of morphine antinociception.
abstract: 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.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global Center of Excellence and Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Okura
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Ozawa
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ito
authors.forename: Midori
authors.initials: M
authors.lastname: Kimura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kagawa
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000465:Algorithms; D000701:Analgesics, Opioid / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D000818:Animals; D019540:Area Under Curve; D001628:Beverages; D032083:Citrus paradisi / Q000737:chemistry*; D004357:Drug Synergism; D004361:Drug Tolerance; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects*; D011802:Quinidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000701:Analgesics, Opioid; D009020:Morphine; D011802:Quinidine