Printed in U.S.A. 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, a-naltrexol. and fl-naltrexol as tnimethylsilyl derivatives. Analysis of urine from rabbit, monkey, and rat demonstrated that, like man, these species reduce naltrexone primarily to /3-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 /9-naltrexol (16.8%). and conjugated 9-naItrexol (1 1,8%), Thirty-four percent of the dose appeared in 0-24 hr and 3 % during 24-48 hr. The ratio of /3-naltrexol to naltrexone rose from 2 at 0-4 hr to 34 at 24-48 hr. Monkeys receiving a daily dose of 12 mg/kg po. chronically. excreted very little free fl-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 83 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 fl-naltrexol is produced as a urinary metabolite, othe