Placental transfer of chloroquine in pregnant rabbits.

The pharmacokinetics of chloroquine was determined in pregnant and nonpregnant rabbits following intravenous administration. Blood concentrations of chloroquine and desethylchloroquine in the mother and fetuses were assayed using HPLC. Chloroquine rapidly crossed the placenta, resulting in equivalent fetal and maternal blood concentrations 15-30 min after dosing the mother. The subsequent 1 and 2 hr fetal blood concentrations were about two-fold higher than the corresponding maternal blood concentrations. The desethylchloroquine metabolite blood concentrations were low relative to the drug, although the metabolite was detected in all blood samples including the initial 5 min maternal blood samples and 15 min fetal blood samples. Comparing the pharmacokinetics of chloroquine in the pregnant and nonpregnant animals revealed no difference in total body clearance. However, there was an approximately two-fold decrease in the apparent volumes of distribution and terminal half life in the pregnant rabbits. Because of the relatively large inter-animal variability in these parameters, the differences were not statistically significant (p greater than 0.05), but do indicate a trend toward changes in chloroquine pharmacokinetics during pregnancy.