Pharmacokinetic changes during pregnancy and their clinical relevance.

The dynamic physiological changes that occur in the maternal-placental-fetal unit during pregnancy influence the pharmacokinetic processes of drug absorption, distribution and elimination. Pregnancy-induced maternal physiological changes may affect gastrointestinal function and hence drug absorption rates. Ventilatory changes may influence the pulmonary absorption of inhaled drugs. As the glomerular filtration rate usually increases during pregnancy, renal drug elimination is generally enhanced, whereas hepatic drug metabolism may increase, decrease or remain unchanged. A mean increase of 8 L in total body water alters drug distribution and results in decreased peak serum concentrations of many drugs. Decreased steady-state concentrations have been documented for many agents as a result of their increased clearance. Pregnancy-related hypoalbuminaemia, leading to decreased protein binding, results in increased free drug fraction. However, as more free drug is available for either hepatic biotransformation or renal excretion, the overall effect is an unaltered free drug concentration. Since the free drug concentration is responsible for drug effects, the above mentioned changes are probably of no clinical relevance. The placental and fetal capacity to metabolise drugs together with physiological factors, such as differences acid-base equilibrium of the mother versus the fetus, determine the fetal exposure to the drugs taken by the mother. As most drugs are excreted into the milk by passive diffusion, the drug concentration in milk is directly proportional to the corresponding concentration in maternal plasma. The milk to plasma (M:P) ratio, which compares milk with maternal plasma drug concentrations, serves as an index of the extent of drug excretion in the milk. For most drugs the amount ingested by the infant rarely attains therapeutic levels.