Lorazepam: glucuronide formation in the cat.

The excretion and metabolism of lorazepam was studied in domestic cats. After oral administration of 14-C-lorazepam (1 mg/kg), the mean percent of the dose excreted in urine was 47.3 plus or minus 6.7% (SD) and in feces 54.0 plus or minus 6.1% (SD). The main urinary metabolite was lorazepam glucuronide; its mean excretion over the first 3 days amounted to 29% of the dose (66% of urinary radioactivity). When 20 mg of unlabeled drug per kg was given, about 40% of the dose was excreted into urine as lorazepam glucuronide within 6 days. Conculsive evidence for the glucuronide structure was obtained by chemical analysis and mass spectrometry of the lorazepam conjugate isolated from cat urine. The radioactivity in urine which was not attributable to several minor metabolites. In plasma, both lorazepam and lorazepam glucuronide were present. These findings indicate that the cat is capable of using glucuronidation as a major route of conjugation, contrary to the many reports that cats conjugate exogenous materials poorly with glucuronic acid.