DISPOSITION AND BIOTRANSFORMATION OF QUINPIROLE, A NEW D-2 DOPAMINE AGONIST ANTIHYPERTENSIVE AGENT, IN MICE, RATS, DOGS, AND MONKEYS

The disposition and metabolism of quinpirole were studied in rats, mice, dogs, and monkeys. A single 2 mg/kg dose of 1C-quinpirole was administered orally to rats, mice, and monkeys. Dogs were given a single 0.2 mg/kg iv dose of 14C-quinpirole. Of the dose administered, 75-96 % was recovered in the urine within 72 hr, with the majority being excreted during the first 24 hr. Peak plasma concentrations of radioactivity and quinpirole were coincident and were observed within 0.25 hr in rodents and at 2 hr in monkeys. Unchanged quinpirole accounted for 0.9%, 36%, and 69 % respec-tively. Biotransformation of quinpirole was compared by quantitating the urinary metabolites by HPLC. The percentage of the radioactivity in urine representing unchanged drug was determined for each species: monkey (3%), dog (13%), mouse (40%), and rat (57%). The majority of 1C-quinpiroIe was shown to be biotransformed in rats, mice, and monkeys through common metabolic pathways but t