Pharmacokinetics in Neonatal Medicine
The safe and effective use of medications in the neonatal intensive care unit (NICU) requires an understanding of the principles of pharmacokinetics (PK) and pharmacodynamics (PD) that guide individual dosing and aim to provide drug exposures designed for the best clinical outcomes and lowest risk of adverse effects. Significant differences in physiology affect drug absorption, distribution, metabolism, and elimination. Therefore the PK of drugs in neonates is unique and cannot be extrapolated from older children or adults. In the NICU, infants are undergoing dramatic changes in body size, body composition, cardiac output and perfusion, renal and hepatic function, and ontogeny (age-related maturation) of drug metabolizing enzymes. This means that infants in the NICU will exhibit wide variations in drug exposures, and clinicians often need to consider dose adjustments for these differences. Developmental changes in organ systems also influence safety and efficacy of drugs used in infants. Basic knowledge of PK and PD can explain rational dosing across a broad spectrum of prematurity, clinical conditions, treatment interventions, and drug classes. This chapter reviews basic PK and PD principles that will help clinicians understand the drug- and infant-specific factors that explain the variation in PK and drug exposures that are expected among infants in the NICU.
