Drug Kinetics in Childbirth

Drugs from a wide range of pharmacological classes are commonly given to women in childbirth, either for a maternal effect or a fetal/neonatal effect. A number of striking physiological and biochemical changes occur during labour and delivery that might alter drug kinetics. The rate of drug absorption from the gastrointestinal tract may be normal in labour provided that narcotic analgesics are not administered concurrently. Altered blood flow characteristics in the extremities could modify drug absorption from intramuscular injection sites. Drug distribution might be altered as a result of the presence of placental-fetal tissues, or as a consequence of changes in, for example, maternal blood volume, concentrations of proteins and other endogenous compounds, cardiac output or tissue perfusion. Although data are scanty on the status of the physiological determinants of drug clearance, that limited information available suggests that drug clearance could be altered in childbirth. The possibility of a placental and/or fetal contribution should not be overlooked when considering the clearance of drugs administered during labour and delivery. Uterine contractions, maternal posture and obstetric medication have been found to affect the extent of some of the physiological changes that occur. Consequently, drug disposition could be modified by these factors. All of the drugs given to women in childbirth are capable of crossing the placenta to some degree. This is a disadvantage in those cases where drugs are given for a maternal effect and may result in neonatal sequelae. The fetal exposure to, and neonatal burden at delivery of, drugs administered during labour and delivery may be influenced by many factors, including maternal posture, mode of drug administration, the drug administration to delivery interval, fetal pH, and whether intravenous bolus drug administration coincides with the contraction or relaxation phase of uterine activity. Protracted elimination by the neonate may occur for those drugs acquired in utero. Realisation of this is of considerable importance in the clinical management of the newborn.