Understanding the relative roles of pharmacogenetics and ontogeny in pediatric drug development and regulatory science

J Clin Pharmacol. 2010 Dec;50(12):1377-87. doi: 10.1177/0091270009360533. Epub 2010 Feb 11.


Understanding the dose-exposure-response relationship across the pediatric age spectrum from preterm and term newborns to infants, children, adolescents, and adults is a major challenge for clinicians, pharmaceutical companies, and regulatory agencies. Over the past 3 decades, clinical investigations of many drugs commonly used in pediatric therapeutics have provided valuable insights into age-associated differences in drug disposition and action. However, our understanding of the contribution of genetic variation to variability in drug disposition and response in children generally has lagged behind that of adults. This article proposes a systematic approach that can be used to assess the relative contributions of ontogeny and genetic variation for a given compound. Application of the strategy is illustrated using the current regulatory dilemma posed by the safety and effectiveness of over-the-counter cough and cold remedies as an example. The results of the analysis can be used to aid in the design of studies to yield maximally informative data in pediatric populations of different ages and developmental stages and thereby improve the efficiency of study design.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antitussive Agents / adverse effects
  • Antitussive Agents / pharmacokinetics
  • Antitussive Agents / therapeutic use
  • Child
  • Child Development*
  • Child, Preschool
  • Common Cold / drug therapy
  • Cough / drug therapy
  • Drug Design*
  • Drug Evaluation / legislation & jurisprudence*
  • Expectorants / adverse effects
  • Expectorants / pharmacokinetics
  • Expectorants / therapeutic use
  • Genetic Variation*
  • Humans
  • Infant
  • Infant, Newborn
  • Nonprescription Drugs / adverse effects
  • Nonprescription Drugs / pharmacokinetics
  • Nonprescription Drugs / therapeutic use
  • Pharmacogenetics / methods
  • Pharmacokinetics*
  • Research Design*
  • United States
  • United States Food and Drug Administration / legislation & jurisprudence


  • Antitussive Agents
  • Expectorants
  • Nonprescription Drugs