This chapter describes drug therapy in pregnant and nursing women. There are two compelling reasons for studying drugs and drug therapy during pregnancy. The first relates to the changing age of reproduction. The second relates to the physiologic changes that occur with gestation. To accommodate fetal growth and development and provide a measure of safety for the woman, pregnancy alters a woman's underlying physiology. Regional blood-flow changes also occur in pregnant women and can affect drug distribution and elimination. Blood flow increases to the uterus, kidneys, skin, and mammary glands, with a compensatory decrease in skeletal muscle blood flow. Pregnancy is also associated with a partially compensated respiratory alkalosis that may affect the protein binding of some drugs. The clearances of drugs metabolized by cytochrome P450 3A4 (CYP3A4) have been shown to be consistently increased in multiple studies of pregnant women. The hepatic clearance (CLH) of phenytoin, a restrictively eliminated drug that is predominantly a CYP2C9 substrate, increases during pregnancy, thereby resulting in correspondingly lower total plasma concentrations.
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