Neonatal pharmacology: extensive interindividual variability despite limited size

Providing safe and effective drug therapy to neonates requires knowledge of the impact of development on the pharmacokinetics and pharmacodynamics of drugs. Although maturational changes are observed throughout childhood, they are most prominent during the first year of life. Several of these processes overlap, making development an extremely dynamic system in the newborn compared with that in infants, children, or adults. Changes in body composition and porportions, liver mass, metabolic activity, and renal function collectively affect the pharmacokinetic behavior of medications. Instead of simply adapting doses by scaling adult or pediatric doses on the basis of a patient's weight and/or body surface area, integrated knowledge of clinical maturation and developmental pharmacology is critical to the safe and effective use of medications in neonates. Unfortunately, the effects of human ontogeny on both pharmacokinetics and pharmacodynamics have not been well established in these early stages of life, and information regarding the influence of developmental changes on the pharmacodynamics of medications is even more limited. Theoretically, age-dependent variations in receptor number and affinity for drugs have significant potential to influence an individual's response to drug therapy. In this review, some of the relevant covariates of pharmacokinetics and pharmacodynamics in neonates are reviewed and illustrated based on the published literature.