Pharmacokinetics of clearance in the maternal-fetal amniotic fluid system of the rat

Abstract

A pharmacokinetic model of the maternal-fetal amniotic fluid system was designed to permit calculation of clearances from the steady-state concentrations of p-phenylbenzoic acid (PPBA) during infusion of PPBA into the maternal vein and the amniotic fluid of pregnant rats on the 16th to the 21st day of gestation. Transplacental clearance from the fetus to the mother maintained fairly constant values until the 19th day of gestation but decreased on Days 20 and 21 of gestation. Both clearances from the fetus into the amniotic fluid and from the amniotic fluid into the fetus showed higher values during the earlier stages of gestation, indicating that amniotic fluid may play an important role in the pharmacokinetics of PPBA in the fetus during the earlier stage of gestation. Fetal tissue clearance appeared to contribute to the elimination of PPBA in the fetus on Days 20 and 21 of gestation. Transplacental clearance from the mother to the fetus and clearance by nonplacental elimination in the mother increased with the day of gestation. The relationship between developmental changes in clearances and physiological changes in placenta and fetal tissues is discussed. The present model provides a basis for calculation of clearances in the maternal-fetal amniotic fluid system.