How to translate pharmacokinetic data into dosing recommendations
Pharmacotherapy in children is challenging due to limited knowledge of the influence of physiological changes on drug exposure and response. Differences in drug pharmacokinetics are often considered the main drivers of age-related differences in dose requirements in neonates and young infants. Pharmacokinetic parameters in these young children can be derived from a 'population analysis' of drug concentration measurements in the blood at various time points after drug administration. A major advantage of performing a population analysis is that it allows investigations into betweensubject variability. Patient characteristics that can describe patterns in the variability of pharmacokinetic parameters can be used to predict these pharmacokinetic parameters in other patients within the same population. The distribution volume of a drug is the main driver of peak concentrations, whereas drug clearance is the driver of steady state concentrations. Information on how these parameters differ between individuals within a given population therefore allows clinicians to determine drug doses that correct for these differences, leading to the same exposure for each patient. The patient characteristics that predict the variability in pharmacokinetic parameters are called covariates, and the mathematical equations describing their relationship with the pharmacokinetic parameters can be used as the basis for evidence-based pediatric dosing recommendations.