Biotransformation of bromperidol in rat, dog, and man.

The metabolic fate of 14C-bromperidol after po administration was studied in rat, dog, and man. When 14C-bromperidol was given to female Wistar rats, 23-29% of the dose was excreted in the urine and 38-45% in the feces over a 7-day period. In dogs, 39-74% of the administered dose was excreted in the urine and 26-43% in the feces over the same period. In both rats and dogs, bromperidol was extensively metabolized; most of the urinary radioactivity associated with metabolites arose from cleavage of the bromperidol molecule via oxidative N-dealkylation. After administration of 14C-bromperidol to human volunteers, 28-50% of the dose was eliminated in the urine while 18-46% was eliminated in the feces over a 13-day period. Although bromperidol appeared to be extensively metabolized in man, the major portion of the urinary radioactivity (70-75%) was associated with the O-glucuronide conjugate of intact drug. Thus, oxidative N-dealkylation does not appear to be the major urinary metabolic pathway of the drug in man.