Placental Transmission of Chemicals in the Subhuman Primate

I would like to summarize several studies indicating the value of pregnant primate as a model for investigating the metabolism and placental transmission of chemicals from mother to fetus. A drug may be free, bound, or metabolized in the mother. The net effect is that the free drug will have easy access to the fetal circulation; the bound drug will have less access; and, if the maternal liver is metabolizing the administered compound, metabolites may appear in the fetus. In these studies the maternal and fetal circulations of pregnant, subhuman primates were cannulated; and, with the use of isotopically labeled compounds, we traced the capacity of several compounds to traverse the placenta. When 14C-labeled cyclohexylamine (a metabolite of cyclamate) was introduced into the maternal circulation, the amine diffused without difficulty to the fetal circulation, where blood concentrations attained those found on the maternal side. Some of the cyclohexylamine appeared in amniotic fluid. When the infusion was terminated, concentration of the amine declined rapidly in both maternal and fetal circulations.1 When 14C cyclohexylsulfamic acid (cyclamate) was infused into the maternal circulation, there was a remarkable buildup in concentration, with much lower levels observed in the fetal blood.1 This differential was attributed to the fact that cyclohexylsulfamic acid was protein-bound on the maternal side. Nevertheless, some did get into the amniotic fluid. With cessation of infusion, there was a rapid drop in the maternal blood concentration, with a similar fall on the fetal side. Metabolism of the amino acid, monosodium glutamate, occurred on the maternal side, and essentially none of it reached the fetus.2