Methodological issues in the design of paediatric pharmacokinetic studies

A larger number of studies are being conducted in paediatric patients for drug development than has ever occurred previously as a result of the current legislative acts in the US and Europe. Designing paediatric studies requires knowledge of the disposition of the drug or biological product in varying age groups. The methodology for designing pharmacokinetic studies is complex, and involves ethical considerations, planning for the study through modelling and simulation, arranging a sampling schedule that meets the requirements of the analysis and the study population, and considering the special groups of patients within the paediatric population. Planning for a paediatric pharmacokinetic study involves important decisions on sample size and sampling schedule to estimate the pharmacokinetic parameters of interest. Ideally, the pharmacokinetic variability should guide these decisions on a case-by-case basis. US FDA guidances on paediatric pharmacokinetic studies, exposure-response relationships and population pharmacokinetics, all provide a basis to make some of the critical decisions in designing a paediatric pharmacokinetic study. These considerations are reviewed in this article and should assist drug developers in improving the design of paediatric pharmacokinetic studies in the future.