The effect of repeated i.v. administration of
cocaine HCl (1.5, 3 or 6 mg/kg daily) from gestational day 8 through gestational day 18 was studied on maternal and litter parameters in the pregnant female Sprague-Dawley rat. These doses of
cocaine had no significant effect on
maternal weight gain or nutritional intake and did not significantly affect litter size. Levels of
cocaine and its metabolite
benzoylecgonine in the brain and plasma of the dams and their fetuses were measured on gestational day 18 at 1, 5, 20 or 60 min after a single injection or 11 daily i.v.
injections of
cocaine (6 mg/kg). The shape of the time courses for
cocaine differed somewhat between dams and fetuses, with fetal plasma concentrations of
cocaine initially being lower than those of their dams and then by 5 min becoming equivalent to those of their dams. Although plasma concentrations of
cocaine soon equilibrated between dams and fetuses, plasma concentrations of
benzoylecgonine did not. Interestingly, brain concentrations of
cocaine did not differ between dams and fetuses. The most remarkable finding was that the relative distribution of
cocaine between brain and plasma differed after chronic vs. acute treatment, with a relative shift in the distribution of
cocaine from plasma to the brain in the fetuses, and with the exception of the earliest time point measured, in the dams after repeated dosing.