Physiological alterations during pregnancy: impact on toxicokinetics.

The physiological changes that occur in the alimentary, cardiovascular, pulmonary, and renal organ systems during pregnancy are designed to increase availability of nutrients to and remove wastes from the fetus. Although this is a general requirement, not all animals use the same strategies to meet these goals. These physiological adaptations will impact on toxicokinetics and may alter toxicodynamics. Absorption, distribution, metabolism, transfer between maternal and fetal compartments, and elimination will change for many xenobiotics during pregnancy. The changes in body weight, total body water, plasma proteins, body fat, and cardiac output will alter the distribution of many xenobiotics (Hytten and Leitch, 1971; Hytten and Chamberlain, 1980; Mattison, 1986). As the toxicokinetic parameters change across species, it is important to understand their impact on chemicals associated with maternal, placental, and fetal toxicity for appropriate cross-species extrapolation.