Misra A L, Bloch R, Vardy J, Mulé S J, Verebely K
Drug Metab Dispos. 1976 May-Jun;4(3):276-80.
After injection of (15,16-3H)naltrexone (10 mg/kg s.c.) in male Wistar rats, peak concentrations 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 metabolities were present in brain and plasma at longer time periods. The t1/2 of naltrexone in brain and plasma were approximately 8.0 and 11.4 hr. respectively. The brain/plasma ratios of naltrexone at earlier times (0.5-1 hr) were higher than those at later times. The binding of naltrexone in vitro with rat plasma proteins in concentrations of 1-10 mug/ml ranged between 41 and 59% 6beta-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-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 metabolites.
给雄性Wistar大鼠皮下注射(15,16 - 3H)纳曲酮(10毫克/千克)后，药物在0.5小时内于脑和血浆中达到峰值浓度。纳曲酮水平在脑内2至24小时维持稳定，48小时时几乎检测不到。较长时间段后，脑和血浆中存在大量代谢物。纳曲酮在脑和血浆中的半衰期分别约为8.0小时和11.4小时。早期（0.5 - 1小时）纳曲酮的脑/血浆比值高于后期。纳曲酮在体外与浓度为1 - 10微克/毫升的大鼠血浆蛋白的结合率在41%至59%之间。6β-纳曲醇在脑中含量极少，但在血浆中未检测到。除了7,8 - 二氢 - 14 - 羟基去甲吗啡酮和7,8 - 二氢 - 14 - 羟基吗啡外，在脑中还初步获得了纳曲酮的其他三种代谢物的证据。除了游离和结合的纳曲酮及其N - 脱烷基代谢物外，这些代谢物也存在于血浆中。
