The urinary excretion profiles of naltrexone in man, monkey, rabbit, and rat.
A gas-chromatographic method has been developed for the simultaneous determination of naltrexone, alpha-naltrexol, and beta-naltrexol as trimethylsiyl derivatives. Analysis of urine from rabbit, monkey, and rat demonstrated that, like man, these species reduce naltrexone primarily to beta-naltrexol. In naltrexone maintenance patients receiving 125 mg po three times per week, an average of 37% of the dose was recovered in 48-hr urine as free naltrexone (0.8%), conjugated naltrexone (7.6%), free beta-naltrexol (16.8%), and conjugated beta-naltrexol (11.8%). Thirty-four percent of the dose appeared in 0-24 hr and 3% during 24-48 hr. The ratio of beta-naltrexol to naltrexone rose from 2 at 0-4 hr to 34-48 hr. Monkeys receiving a daily dose of 12 mg/kg po, chronically, excreted very little free beta-naltrexol and exhibited an apparent sex-related difference in excretion patterns, with females excreting more than twice as much total base as males. Rabbits given a dose of 30 mg/kg ip for 4 days excreted conjugated naltrexone as the predominant urinary metabolite, accounting for 80% of total base recovered in 24 hr. In rats receiving 100 mg/kg po, less than 1% of the administered dose could be accounted for in the 24-hr urine, indicating that although the beta-naltrexol is produced as a urinary metabolite, other means of disposition of the drug must exist. Thus, in man and the monkey, beta-naltrexol is the predominant and persistent urinary metabolite. Urinary excretion profiles of naltrexone differ greatly between species commonly examined for chronic toxicity studies.
D000284:Administration, Oral; D000328:Adult; D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D004334:Drug Administration Schedule; D005260:Female; D000882:Haplorhini; D006801:Humans; D007274:Injections, Intraperitoneal; D008253:Macaca mulatta; D008297:Male; D008722:Methods; D009270:Naloxone / Q000031:analogs & derivatives*; D009271:Naltrexone / Q000008:administration & dosage / Q000652:urine*; D011817:Rabbits; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity
D009270:Naloxone; D009271:Naltrexone