On the pharmacokinetics of domperidone in animals and man. I. Plasma levels of domperidone in rats and dogs. Age related absorption and passage through the blood brain barrier in rats.

Domperidone, a novel gastrokinetic and antinauseant lacking central side-effects, was administered intravenously to male Wistar rats and orally to fasted rats of either sex and to 1- and 6-day old neonates at doses of 2.5 mg 14C-labelled drug/kg. The biphasic absorption of domperidone in fasted rats was extremely rapid suggesting a partial absorption from the stomach. The metabolism of domperidone was sex- and age-related: it was slower in the female rat and in the neonates. The elimination system for the metabolites was still immature in the 1-day old pups. The distribution of domperidone (and related metabolites) to the rat brain was limited, brain concentrations being lower than corresponding plasma levels in all cases. In 1-day old neonates, the blood-brain barrier was less obstructive to the passage of domperidone than in older rats. In Beagle dogs, domperidone pharmacokinetics were described by a two-compartment model with half-lives of distribution and elimination of 6 minutes and 2.45 hours respectively. The time-courses of the drug plasma levels were similar for single and repeated (once daily for 11 months) doses of 2.5, 10 and 40 mg/kg, indicating that chronic administration of domperidone, even at high dose levels, did not alter its pharmacokinetics. AUC-values increased proportionally with the dose pointing to linear pharmacokinetics over a wide dose range.