The excretion and metabolism of the novel gastrokinetic and antinauseant drug domperidone were studied after oral administration of the14C-labelled compound to rats, dogs and man, and after intravenous administration to rats and dogs.
Excretion of the radioactivity was almost complete within four days. In the three species, the radioactivity was excreted for the greater part with the faeces. Biliary excretion of the radioactivity amounted to 65% of the dose 24 hours after intravenous administration in rats.
Unchanged domperidone as determined by radioimmunoassay, accounted in urine for 0.3% in dogs, 0.4% in man, and in faeces for 9% in dogs and 7% in man. The main metabolic pathways of domperidone in the three species were the aromatic hydroxylation at the benzimidazolone moiety, resulting in hydroxy-domperidone -the main faecal metabolite-, and the oxidativeN-dealkylation at the piperidine nitrogen, resulting in 2,3-dihydro-2-oxo-1H-benzamidazole-1-propanoic acid the major radioactive urinary metabolite- and 5-chloro-4-piperidinyl-1,3-dihydro-benzimidazol-2-one. In urine the two first metabolites were present partly as conjugates.
A mass balance for the major metabolites in urine, faeces, bile and plasma samples was made up after radio-HPLC (reversephase HPLC with on-line radioactivity detection) of various extracts. Only minor species differences were detected.