The comparative metabolism of zolazepam in rat, dog and monkey

The metabolic disposition.of zolazepam, a pyrazolodiazepinone, was studied in male and female Spartan rats, Beagle dogs and Rhesus monkeys. Six principal urinary metabolites were characterized by gas chromatography and combined gas chromatography-mass spectrometry. The major metabolite in male and female rats was produced by N-demethylation and hydroxylation. In addition, female rats, but not the male demethylated zolazepam at the 1-position. Male and female dogs also demethylated zolazepam in the 1-position and hydroxylated in a position other than C-6, producing a metabolite peculiar to the dog. In marked contrast, the major metabolite in the monkey involved demethylation without subsequent hydroxylation.