Principles of Neonatal Pharmacology

Abstract

The pharmacologic behavior of drugs administered to newborns shows unique characteristics which in general cannot be extrapolated from data derived from older infants and adults. Rapidly changing physiological processes characteristic of the neonatal period may profoundly affect the pharmacokinetics of drugs and result either in subtherapeutic or toxic drug concentrations. Therefore, the pharmacokinetics but also the safety and efficacy of drugs need to be determined by trials specifically designed to include term and preterm infants. Since the 1950s investigators have reported serious side effects associated with the inadvertent use of drugs in newborns. Sulfonamides displaced bilirubin from albumin-binding sites which resulted in an increased incidence of kernicterus in preterm infants. The “grey baby syndrome” was described in three newborns treated with chloramphenicol. The occurrence of cardiovascular collapse and shock in these neonates was due to the accumulation of free drug caused by deficient glucuronidation in the presence of a reduction in glomerular filtration. More recent examples of the consequences of ignorance about the unique transitional metabolic and physiological characteristics of neonates are easily found. These include poisoning of very low birth weight infants by inadvertent exposure to toxic doses of benzyl alcohol contained in bacteriostatic water or saline used to reconstitute medications or to flush intravascular catheters, and the excessive mortality associated with the intravenous administration of vitamin E to low birth weight infants.