In stark contrast to adults, the use of drugs in infants, children and adolescents embodies a unique element which must be considered to ensure drug safety and efficacy; namely, the impact of development on both drug disposition and action.

Development, per se, represents a continuum of biologic events that enables adaptation, somatic growth, neuro-behavioral maturation and eventually, reproduction. The impact of development on the disposition of a given drug is determined, to a great degree, by age-associated changes in body composition (e.g. body water spaces, circulating plasma protein concentrations) and the acquisition of function of organs and organ systems which are important in determining drug metabolism (e.g. the liver) and excretion (e.g. the kidney). While it is often convenient to classify pediatric patients on the basis of postnatal age for the provision of drug therapy (e.g. neonate≤1 month of age; infant= 1–24 months of age: children=2–12 years of age; and adolescents=12–18 years of age), it is important to recognize that the changes in physiology which characterize development may not correspond to these age defined ‘breakpoints’. In fact, the most dramatic changes in drug disposition occur during the first 18 months of life where the acquisition of organ function is most dynamic. Additionally, it is important to note that the pharmacokinetics of a given drug may be altered in pediatric patients consequent to intrinsic (e.g. gender, genotype, ethnicity, inherited diseases) and/or extrinsic (e.g. acquired disease states, xenobiotic exposure, diet) factors which may occur during the first two decades of life.

In addition to the physiological and psychological development that is quite evident during the first two decades of life, it is apparent that ontogeny can also have a profound impact on drug action. While current information rarely permits one to profile a predictable relationship between age and pharmacodynamics, age-associated differences in the dose versus concentration versus effect relationship are evident for many therapeutic drugs. It is not known, however, whether these differences represent discrete and definable ‘events’ associated with drug receptor interaction (e.g. receptor number/density, affinity, kinetics of association/dissociation) or alternatively, age related differences in the complex milieu of post receptor biochemical events (e.g. the availability and residence of second messengers, the number and types of G-proteins, alterations in transmembrane ion flux capable of altering activity of channel-linked receptors, etc.).

For a practitioner to develop a rational and sound pharmacotherapeutic approach to the pediatric patient, it is essential that he or she considers the developmental ‘factors’ (physiological, psychological and pharmacological) that make infants, children and adolescents different from adults. It is the goal of this chapter to provide the reader not with a drug-specific overview of pediatric clinical pharmacology but rather, a premise upon which to consider the potential impact (both therapeutic and toxicologic) of ontogeny on drug disposition and action.