DISPOSITION OF [15,16-H-3]NALTREXONE IN CENTRAL NERVOUS-SYSTEM OF RAT

  • 1 January 1976
    • journal article
    • research article
    • Vol. 4  (3) , 276-280
Abstract
After injection of 10 mg/kg s.c. [15,16-3H]naltrexone [a potent narcotic antagonist having therapeutic advantages over other antagonists in the ambulatory treatment of opiate addicts] in male Wistar rats, peak concentrations of drug occurred in brain and plasma within 0.5 h. Levels of naltrexone were sustained in brain between 2 and 24 h and were barely detectable at 48 h. Significant amounts of metabolites were present in brain and plasma at longer time periods. The t1/2 [half-time] of naltrexone in brain and plasma were approximately 8.0 and 11.4 h, respectively. The brain/plasma ratios of naltrexone at earlier times (0.5-1 h) were higher than those at later times. The binding of naltrexone in vitro with rat plasma proteins in concentrations of 1-10 .mu.g/ml ranged between 41 and 59%. 6.beta.-Naltrexol was present in very small amounts in brain but not in plasma. In addition to 7,8-dihydro-14-hydroxynormophinone and 7,8-dihydro-14-hydroxynormophinone, tentative evidence was obtained for 3 other metabolites of naltrexone in brain. These metabolites were also present in plasma in addition to free and conjugated naltrexone and its N-dealkylated metabolites.