Drug Kinetics in Pregnancy

Abstract

Any drug given to a pregnant woman must be considered as possibly harmful in the fetus, since all drugs administered to the mother cross the placental membrane, although at different rates. Important physiological changes occur in pregnancy, which may influence the kinetics of drugs. Differences in gastrointestinal function are likely to alter drug absorption rates in the stomach or gut. Ventilatory alterations modify pulmonary drug absorption or elimination. Important changes in haemodynamics and alterations in body water compartments influence drug distribution and elimination. Renal drug elimination is generally enhanced, whereas hepatic drug elimination may be modified in different ways. Computerised pharmacokinetic models representing the compartmental aspects of the fetal-maternal unit and fetal-maternal drug interrelationships may be used to predict kinetic consequences of fetal drug exposure. Such information may be a useful guide for the clinical use of drugs during pregnancy, particularly for treatment of fetal disease.

Pharmacokinetics of Prophylactic Cefazolin in Parturients Undergoing Cesarean Delivery

“…In pregnancy, a substantial percentage of the weight gain is attributed to increased total body water, of which approximately 80% is extracellular (41). Therefore, pregnancy may be associated with increased drug dilution.…”

Paracetamol metabolism in pregnancy.

“…It is now apparent that the physiological and biochemical changes occurring during pregnancy may influence drug metabolism (Cummings, 1983;Krauer & Krauer, 1977). However, published studies to date have largely investigated the effect of pregnancy on the elimination of renally cleared drugs and drugs metabolised by the hepatic mixed function oxidase system (Cummings, 1983).…”

Population Pharmacokinetics of Rifampin in Pregnant Women with Tuberculosis and HIV Coinfection in Soweto, South Africa

“…It is deacetylated in the liver and is excreted in the bile and urine (18). While hepatic cholestasis related to the use of estrogens like ethynylestradiol can interfere with the elimination of some drugs that are cleared via the biliary route (19) and may theoretically affect rifampin clearance (20), the effects of pregnancy on rifampin pharmacokinetics have not been investigated. Further, rifampin is known to cross the placenta; however, exposures of the fetus and neonate to this drug, which is a strong inducer of metabolizing enzymes that may theoretically affect exposures of drugs administered to neonates, have been poorly characterized (21,22).…”