Physiologic changes in pregnancy and their effect on drug disposition.

Changes in maternal physiology occur normally during pregnancy and have the potential to alter the absorption, distribution, and elimination of drugs used therapeutically in pregnant women. These physiologic changes include: plasma volume expansion and increases in extracellular fluid space and total body water; decreased plasma albumin concentration; a compensated respiratory alkalosis; increased cardiac output with regional blood flow changes; increased renal blood flow associated with increased glomerular filtration; changes in hepatic drug metabolizing enzymes; and changes in gastrointestinal function. These changes begin in early gestation but are most pronounced in the third trimester of pregnancy. Further maternal physiologic changes occur intrapartum with some normalizing themselves within 24 hours of delivery, while others are sustained only returning to normal some 12 weeks postpartum. These physiologic changes form the basis for the need for pharmacokinetic studies during pregnancy.