Basics and dynamics of neonatal and pediatric pharmacology

Abstract

Understanding the role of ontogeny in the disposition and actions of medicines is the most fundamental prerequisite for safe and effective pharmacotherapeutics in the pediatric population. The maturational process represents a continuum of growth, differentiation, and development, which extends from the very small preterm newborn infant through childhood, adolescence, and to young adulthood. Developmental changes in physiology and, consequently, in pharmacology influence the efficacy, toxicity, and dosing regimen of medicines. Relevant periods of development are characterized by changes in body composition and proportion, developmental changes of physiology with pathophysiology, exposure to unique safety hazards, changes in drug disposition by major organs of metabolism and elimination, ontogeny of drug targets (e.g., enzymes, transporters, receptors, and channels), and environmental influences. These developmental components that result in critical windows of development of immature organ systems that may lead to permanent effects later in life interact in a complex, nonlinear fashion. The ontogeny of these physiologic processes provides the key to understanding the added dimension of development that defines the essential differences between children and adults. A basic understanding of the developmental dynamics in pediatric pharmacology is also essential to delineating the future directions and priority areas of pediatric drug research and development.