Effect of naloxone on pharmacokinetics of morphine in rats

• Published in: Japanese Journal of Pharmacology 1986, Vol.40 (suppl), p.218-218
• Main Authors: Shibanoki, Shinji, Kubo, Taizo, Ishikawa, Koichi
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)59401-X

Effect of naloxone on intracerebral pharmacokinetics of morphine in rats was investigated. Wistar rats, each weighing about 300 g, were injected intravenously morphine (1.25-30 mg/kg) with or without naloxone (1 mg/kg). High performance liquid chromatography with electrochemical detection and organic solvent extraction were used for the quantitative determination of morphine in the plasma and dissected brain regions, the cortex, hippocampus, striatum, hypothalamus, amygdala, midbrain, medulla-oblongata and cerebellum. Concentrations of the drug were significantly lower in the plasma and brain regions obtained from the animals received both morphine and naloxone than those received morphine only. The decreases of the concentrations were about 60% and 44-58% for the plasma and brain regions, respectively. Those results were also observed by the injection of levallorphan (1 mg/kg). Eliminations of the drug from the plasma and brain were accelerated by naloxone. Binding ability of the drug to plasma protein was not affected by naloxone. Morphine decreased significantly elimination rate of bromsulphalein (20 mg/kg, i.v.) from the plasma, while the decrease was also antagonized by naloxone. These results suggest that morphine decreases its own elimination from the body perhaps because of the decrease in hepatic blood flow, and naloxone affects the pharmacokinetics, disposition, of morphine in opioid receptor site. (Preliminary results were presented at the Opioid Symposium, 1985, Tokyo)