Maternal and fetal distribution of drugs in pregnancy.

Abstract

The disposition of drugs in the maternal‐placento‐fetal unit is influenced by several inter‐reacting processes. Placental transfer of pharmacologically active molecules is modulated by characteristics of the drugs (e.g., lipid solubility, degree of ionization at physiologic pH, molecular weight) and properties of the placenta (e.g., maternal and fetal blood flow, drug metabolism, placental age). The distribution of drugs in the fetus may be determined by differences in permeability of specialized membranes (blood‐brain barrier, renal tubule), binding to specific cellular constituents (binding proteins), selective distribution of the fetal circulation, and active secretion of drugs by the yolk sac. In a general sense the pattern of drug distribution in the fetus frequently resembles that of the mother; however unique differences in absolute tissue concentrations of drugs may occur as a result of increased drug transfer rates into specific tissues. Many compounds crossing the placenta initially concentrate in the fetal liver so that levels in systemic fetal blood may be Significantly different from umbilical venous concentrations. Consequently, the detection of unusual patterns of drug distribution in the fetus that may prove useful in assessing the potential hazards of maternal drug therapy will require more comprehensive data than can be provided by umbilical vessel blood concentrations alone.