METABOLISM OF DIAZEPAM BY LIVER MICROSOMAL ENZYMES OF RATS AND MICE

The metabolic pathways by which diazepam and its metabolites are transformed in vitro by rat and mouse liver microsomes were studied in detail. Using a gas chromatographic technique to measure benzodiazepines, it was demonstrated that the predominant reactions were N-demethylation in rat liver microsomes and C3 hydroxylation in mouse liver microsomes. When N-demethyldiazepam or N-methyloxazepam was used as a substrate there was a clear formation of oxazepam. No exazepam was found in vitro when diazepam was incubated with liver microsomes. Some preliminary data indicate that the presence of diazepam inhibits the further hydroxylation of N-demethyldiazepam and the N-demethylation of N-methyloxazepam. © 1969.