Pharmacogenetics in pediatrics - Implications for practice

The goal of rational drug therapy in infants, children, and adolescents is to produce a desired pharmacologic response in an acceptable and predictable manner while minimizing the occurrence of undesired events. The attainment of this goal requires not only an increasing awareness of the need to individualize drug dosing but most importantly a recognition of factors contributing to the interindividual and intraindividual variability in drug disposition and response. The purpose of this article is to acquaint clinicians with the ontogeny of important drug-metabolizing enzymes during childhood by briefly reviewing the interface between pharmacogenetics, developmental physiology, and pharmacokinetics. This article focuses specifically on the contribution of genetic determinants of drug metabolism or biotransformation, as modified by developmental processes, to the heterogeneity observed in the pediatric population. Within this context, relevant examples of clinical consequences of such variability on pediatric pharmacotherapy are presented and discussed.