Children in clinical trials: towards evidence-based pediatric pharmacotherapy using pharmacokinetic-pharmacodynamic modeling

Expert Rev Clin Pharmacol. 2016 Sep;9(9):1235-44. doi: 10.1080/17512433.2016.1198256. Epub 2016 Jun 27.


Introduction: In pediatric pharmacotherapy, many drugs are still used off-label, and their efficacy and safety is not well characterized. Different efficacy and safety profiles in children of varying ages may be anticipated, due to developmental changes occurring across pediatric life.

Areas covered: Beside pharmacokinetic (PK) studies, pharmacodynamic (PD) studies are urgently needed. Validated PKPD models can be used to derive optimal dosing regimens for children of different ages, which can be evaluated in a prospective study before implementation in clinical practice. Strategies should be developed to ensure that formularies update their drug dosing guidelines regularly according to the most recent advances in research, allowing for clinicians to integrate these guidelines in daily practice. Expert commentary: We anticipate a trend towards a systems-level approach in pediatric modeling to optimally use the information gained in pediatric trials. For this approach, properly designed clinical PKPD studies will remain the backbone of pediatric research.

Keywords: PKPD; Pediatrics; clinical trial; dose individualization; evidence-based dose recommendations; maturation; off-label; pharmacotherapy; physiology.

Publication types

  • Review

MeSH terms

  • Age Factors
  • Child
  • Clinical Trials as Topic / methods*
  • Dose-Response Relationship, Drug
  • Evidence-Based Medicine
  • Humans
  • Models, Biological*
  • Off-Label Use
  • Pediatrics
  • Pharmaceutical Preparations / administration & dosage*
  • Practice Guidelines as Topic


  • Pharmaceutical Preparations