The disposition and metabolism of codorphone, 17-cyclopropyl-methyl-4,5 alpha-8 beta-ethyl-3-methoxymorphinan-6-one (I), a new narcotic antagonist, analgesic agent, have been studied in the rat, dog, and man. Rats and dogs were given single 100- and 50-mg/kg po doses, respectively, of I-3H; human volunteers received single 10- to 30-mg doses of unlabeled I po. The compound appeared to be well absorbed in the three species. In rats the highest levels of radioactivity were in liver, adrenals, kidneys, spleen, and lungs. Excretion was primarily fecal in rats and dogs. In man about 50% of the dose appeared in the 24-hr urine. I was about 95% metabolized by each species. The major metabolites in rats resulted from 3- and/or 17-dealkylation. Metabolism in dogs was characterized primarily by 17-dealkylation. The major pathways of I metabolism in man were 17-dealkylation and 6-reduction. In the three species significant glucuronic acid conjugation of metabolites occurred.
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