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Population clinical pharmacology of children: general principles

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Abstract

Introduction

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.

Discussion

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.

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Abbreviations

CL:

clearance

ka:

absorption rate constant

Ln:

natural logarithm

NONMEM:

Nonlinear mixed-effects model

PD:

pharmacodynamics

PK:

pharmacokinetics

Tabs:

absorption half time

TDM:

therapeutic drug monitoring

V:

volume of distribution

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Correspondence to Brian J. Anderson.

Additional information

Financial Support: The clinical research of K. Allegaert is supported by the Fund for Scientific Research, Flanders (Belgium) with a Clinical Doctoral Grant (A 6/5-KV-G 1).

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Anderson, B.J., Allegaert, K. & Holford, N.H.G. Population clinical pharmacology of children: general principles. Eur J Pediatr 165, 741–746 (2006). https://doi.org/10.1007/s00431-006-0188-y

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