Pharmacokinetics in the ovine maternal-fetal unit.

Abstract

Our primary concern in the use of drugs during pregnancy is the adverse effects that these drugs may produce on the developing fetus. It is now evident that the placenta does not act as a barrier to protect the fetus against exposure to most drugs consumed by the mother during pregnancy. The intensity of drug effects in the fetus or the neonate is a function of the extent of fetal exposure to the drug following maternal administration, and the pharmacodynamic actions of the drug on the mother and fetus. For drugs which have similar pharmacodynamic actions in the maternal-fetal unit, the magnitude of pharmacologic effects will be greatly influenced by the pharmacokinetics of their disposition in the maternal-fetal unit. Information on maternal-fetal pharmacokinetics in humans has been restricted for both technical and ethical reasons, and available data are limited to single time point determinations of maternal and fetal drug concentrations at the time of delivery. Serial determinations of maternal and fetal drug concentrations over time are also not practical in the smaller laboratory animals. Most of the currently available information on maternal-fetal phar­ macokinetics has been obtained using the pregnant ewe. The major advan­ tage of the ewe is the relatively large size of the fetus. The fetal lamb in the third trimester is large enough to permit the implantation of catheters in the fetal blood vessels, making it possible to obtain fetal blood samples without sacrificing the animal. Initially, most studies were carried out with the ewe under anesthesia. However, increasing recognition that maternal