同位体による薬物代謝の研究(第10報)ベンゼン核三重水素標識の安定性

概要

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Basic studies were made on the applicability of a drug labeled with deuterium in the benzene ring for the metabolic study in man. After oral administration of l-ephedrine [arom. U-^3H, α-^<14>C] or l-ephedrine[p-^3H, α-^<14>C] to a rat or incubation with rabbit liver slices, the metabolites were separated and purified to a constant ^3H/^<14>C ratio. The percentage retention of tritium in each metabolite was calculated. Significant isotope effect of tritium was observed at the synthetic step where a propionyl group was introduced by the Friedel-Crafts reaction. Neither noticeable tritium loss nor isotope effect was observed in the formation of metabolites which were produced by the metabolic changes on the side-chain moiety of the substrate. This result supports the expected applicability. A near compete NIH shift of the label was observed during hydroxylation reactions. Percentage retention of tritium (over 90% in each case) was found with p-hydroxyephedrine. ^3H/^<14>C ratios of the glucuronide of p-hydroxyephedrine and p-hydroxyephedrine regenerated from the glucuronide were found to possess a significantly 1ower^3H/^<14>C ratio.
1974-07-25