METABOLISM AND DISPOSITION OF NALTREXONE IN MAN AFTER ORAL AND INTRAVENOUS ADMINISTRATION

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  • 1 January 1981
    • journal article
    • research article
    • Vol. 9  (4) , 369-375
Abstract
Naltrexone is a potent narcotic antagonist which was proposed for the treatment of opiate dependence. The metabolism and elimination of [15,16-3H2]naltrexone was studied in man after oral and i.v. administration. The same metabolites, but in varying proportions, were observed in both cases; conjugated naltrexone and conjugated and unconjugated 6.beta.-naltrexol were the major metabolites observed in plasma, urine and feces. 2-Hydroxy-3-O-methyl-6.beta.-naltrexol was found in minor quantities. Naltexone was almost completely absorbed after oral administration. After oral and i.v. administration of naltrexone, .apprx. 60% of the dose was recovered in the urine in 48 and 72 h, respectively. The route of administration did not significantly affect urinary clearance values obtained for unconjugated or conjugated naltexone and 6.beta.-naltrexol. The route of administration significantly affected terminal plasma half-life values obtained for unconjugated naltrexone (2.7 h, i.v.; 8.9 h, oral), but had little effect on comparable values obtained for total drug, conjugated naltrexone and unconjugated and conjugated 6.beta.-naltrexol. Combined gas chromatography-mass spectrometry was used to validate the presence of naltrexone, 6.beta.-naltrexol and 2-hydroxy-3-O-methyl-6.beta.-naltrexol in urine.