Abstract
The metabolic fates of C14-iproniazid and of C14-isocarboxazid in human subjects were investigated and compared with those previously determined in rats.
Both drugs were rapidly absorbed after oral administration of therapeutic doses.
C14-iproniazid was metabolized by oxidation of the labeled isopropyl substituent resulting in the elimination of 50 to 60% of the radioactive dose as pulmonary carbon dioxide within 24 hours. The oxidation rates differed markedly between individuals as did the patterns of the radioactive urinary excretion products.
C14-isocarboxazid was metabolized analogously by oxidation of the labeled benzyl moiety to C14-benzoic acid which was excreted as urinary C14-hippurate and accounted for 56% of the dose in 24 hours.
Comparison of the fate of the two drugs in man with that in rats revealed identical major pathways of oxidative degradation but characteristic differences of the degradation rates. In both species isocarboxazid seemed to be oxidized faster than iproniazid while faster rates of oxidation of both drugs in the rat than in man were indicated.
Based on certain assumptions a possible relationship is indicated between metabolism and pharmacological effect of the two analogs in the two species.
Footnotes
- Received June 5, 1962.
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