Abstract
The previously reported in vitro metabolism of medazepam to diazepam on incubation with 9000 x g supernatant of rat liver was further investigated. This conversion was found to proceed via the fornmation of 2-hydroxymedazepam. which was delmydrogenated to diazepam. Time latter reaction, oxidation of an alcohol, was unusual in that it was mediated primarily by an enzyme located in the microsomes rather than in the soluble fraction of rat liver. The dog liver 9000 x g supernatant did not form significant amounts of diazepam from medazepam because this dehyclrogenation of 2-hydroxymedazepam was almost completely absent. Instead, N-demethylation of this intermediate was preferred. The in vivo metabolism of medazepam to 2-hydroxymedazepam and diazepam in time rat was consistent with that found in vitro. In the dog, however, the in vivo formation of a diazepam metabolite was observed.
Footnotes
- Received July 23, 1971.
- Accepted September 23, 1971.
- © 1972, by The Williams & Wilkins Company
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