Physiologically Based Pharmacokinetic Models in Developmental Toxicology

The kinetics of disposition of drugs and environmental chemicals will be altered as a result of the rapid and pronounced anatomic and physiologic changes that occur during pregnancy. These include changes in maternal intestinal motility, pulmonary tidal volume and minute volume, cardiac output, and renal function as well as in maternal tissue and fluid volumes and in the weight of the embryo/fetus and its developing organs. Physiologically-based models of pregnancy are capable of taking these temporal changes into account. Several such models have been developed. They vary in their characteristics, depending on the chemical under consideration and the period of gestation of concern to the developers of the models. Several physiologically-based models of gestation are outlined, and an example is given of the application of a physiologically-based model of gestation to predict dose to the rat and mouse fetus.