Pharmacokinetics of verapamil in New Zealand white rabbits during ontogeny

The pharmacokinetics of verapamil during ontogeny in rabbits and in vitro verapamil demethylase activity have been investigated in the liver and whole blood. In vivo experiments revealed that the slope of the postdistributive phase as well as the area under the curve and clearance showed significant differences when newborn and adult rabbits were compared. Other pharmacokinetic parameters, such as volume of distribution and plasma protein binding did not show any statistical differences. Liver microsomal preparation samples from 1-, 8- and 16-day-old rabbits displayed approximately 20% of the activity observed in adults. A significant verapamil demethylase activity in the whole blood of rabbits was also noted. The in vivo results show that newborn rabbits have a capacity to eliminate verapamil that is similar or even higher than that of adults. These findings could not be explained with regard to the in vitro liver metabolism of verapamil, although they could with respect to blood metabolism.