Disposition and urinary metabolic pattern of cabergoline, a potent dopaminergic agonist, in rat, monkey and man

1. The disposition and urinary metabolic pattern of 14C-cabergoline was studied in rat, monkey and man after oral administration of the labelled drug. 2. In all species radioactivity was mainly excreted in faeces, with urinary excretion accounting for 11, 13 and 22% of the dose in rat, monkey and man, respectively. 3. After oral treatment, biliary excretion of radioactivity in rat accounted for 19% of the dose within 24 h. 4. Unchanged drug in 0-24-h urine samples of rat, monkey and man amounted to 20, 9 and 10% of urinary radioactivity, respectively. In the 24-72-h urine samples of all species the relative percentage of unchanged drug increased compared with that measured in the 0-24-h urine. 5. The main metabolite was the acid derivative (FCE21589), which in 0-24-h urine samples of rat, monkey and man accounted for 30, 21 and 41% of urinary radioactivity, respectively. 6. Other metabolites identified in urine of all species resulted from hydrolysis of the urea moiety, the loss of the 3-dimethylaminopropyl group and the deallylation of the piperidine nitrogen.