European Journal of Pediatrics

, Volume 165, Issue 11, pp 741–746 | Cite as

Population clinical pharmacology of children: general principles

  • Brian J. Anderson
  • Karel Allegaert
  • Nicholas H. G. Holford



Population modelling using mixed-effects models provides a means to study variability in drug responses among individuals representative of those for whom the drug will be used clinically.


The advantages of these models in paediatric studies are that they can be used to analyse sparse data, sampling times are not crucial and can be fitted around clinical procedures and individuals with missing data may still be included in the analysis. The introduction of explanatory covariates explains the predictable part of the between-individual variability. Simulations using parameter estimates and their variability can be used to investigate large numbers of children – many more than is possible in studies dealing with real children – for a fraction of the cost, which is an advantage when developing clinical trials. Paediatric population modelling has expanded greatly in the past decade and is now a routine procedure during the development and investigation of drugs. Children have benefitted and will continue to benefit from this approach.


Allometry Children Pharmacodynamics Pharmacokinetics Population modelling 





absorption rate constant


natural logarithm


Nonlinear mixed-effects model






absorption half time


therapeutic drug monitoring


volume of distribution


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Brian J. Anderson
    • 1
    • 4
  • Karel Allegaert
    • 2
  • Nicholas H. G. Holford
    • 3
  1. 1.Department of AnaesthesiologyUniversity of AucklandAucklandNew Zealand
  2. 2.Neonatal Intensive Care UnitUniversity Hospital GasthuisbergLeuvenBelgium
  3. 3.Department of Pharmacology and Clinical PharmacologyUniversity of AucklandAucklandNew Zealand
  4. 4.C/-PICUAuckland Children’s HospitalAucklandNew Zealand

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