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 o f drug absorption, distribution and elimination. Pregnancy-induced mat ernal physiological changes may affect gastrointestinal function and h ence drug absorption rates. Ventilatory changes may influence the pulm onary absorption of inhaled drugs, As the glomerular filtration rate u sually increases during pregnancy, renal drug elimination is generally enhanced, whereas hepatic drug metabolism may increase, decrease or r emain unchanged. A mean increase of SL in total body water alters drug distribution and results in decreased peak serum concentrations of ma ny drugs. Decreased steady-state concentrations have been documented f or many agents as a result of their increased clearance, Pregnancy-rel ated hypoalbuminaemia, lending to decreased protein binding, results i n increased free drug fraction. However, as more free drug is availabl e for either hepatic biotransformation or renal excretion, the overall effect is an unaltered free drug concentration. Since the free drug c oncentration is responsible for drug effects, the above mentioned chan ges are probably of no clinical relevance. The placental and fetal cap acity to metabolise drugs together with physiological factors, such as differences acid-base equilibrium of the mother versus the fetus, det ermine the fetal exposure to the drugs taken by the mother. As most dr ugs are excreted into the milk by passive diffusion, the drug concentr ation in milk is directly proportional to the corresponding concentrat ion 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 in gested by the infant rarely attains therapeutic levels.