Caffeine disposition in the pregnant rabbit. I. Pharmacokinetics following administration by intravenous bolus and continuous zero-order infusion.

We studied the pharmacokinetics of caffeine in the pregnant New Zealand White rabbit, using two methods of drug administration. Ten rabbits that received a continuous intravenous infusion of caffeine (8-22 mg/kg.day) through 29 days of gestation exhibited increased plasma concentrations of caffeine and paraxanthine, its major metabolite, in the last half of gestation. Three rabbits that received intermittent intravenous bolus doses of caffeine (40 mg) exhibited areas under the caffeine plasma concentration versus time curve at 29 days of gestation that were 85-165% greater than those observed before mating. The results of these studies indicate that the elimination of caffeine is diminished in late gestation in the rabbit.