DISPOSITION OF 115,16-3H]NALTREXONE IN THE CENTRAL NERVOUS SYSTEM OF THE RAT

After injection of 1 5, 1 6-3H Jnaltrexone (1 0 mg/kg s.c.) in male Wistar rats, peak concentra-tions of drug occurred in brain and plasma within 0.5 hr. Levels of naltrexone were sustained in brain between 2 and 24 hr and were barely detectable at 48 hr. Significant amounts of metabo-lites were present in brain and plasma at longer time periods.The t of naltrexone in brain and plasma were approximately 8.0 and 1 1.4 hr. respectively. The brain/plasma ratios of naltrexone at earlier times (0.5-i hr) were higher than those at later times. The binding of naltrexone in vitro with rat plasma proteins in concentrations of 1-10 mg/ml ranged between 41 and 59%. 6fl-Naltrexol was present in very small amounts in brain but not in plasma. In addition to 7,8-dihydro-1 4-hydroxynormophinone and 7.8-dihydro-1 4-hydroxynormophine. tentative evidence was obtained for three other metabolites of naltrexone in brain. These metabolites were also present in plasma in addition to free and conjugated naltrexone and its N-dealkylated me-tabolites. Because of the low incidence of undesirable side effects, lack of toxicity, high degree of patien