Population clinical pharmacology of children: general principles
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- Anderson, B.J., Allegaert, K. & Holford, N.H.G. Eur J Pediatr (2006) 165: 741. doi:10.1007/s00431-006-0188-y
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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.
KeywordsAllometry Children Pharmacodynamics Pharmacokinetics Population modelling
absorption rate constant
Nonlinear mixed-effects model
absorption half time
therapeutic drug monitoring
volume of distribution