| Most of the processes underlying drug exposure and response are susceptible to continuous changes, this is especially prominent in (very young) children, in which enzyme pathways, and expression and function of receptors and (target) proteins are still developing. In addition, body size, bodyweight, and body surface area are continuously changing in this group. Unfortunately, due to the lack of clinical research performed in the paediatric population information on pharmacokinetics and the concentration-effect relationship as well as the sources of variability in these areas remain largely unidentified in this population. This results in drug regimens being usually empirically extrapolated from adult regimens instead of drug therapy being tailored for the paediatric population based on differences in physiology and function. The aim of my study project is therefore to develop an approach to optimize and individualize dosing regimens for the paediatric population, using population pharmacokinetic and pharmacodynamic modelling. I aim to characterize the influence of developmental changes on pharmacokinetics, efficacy and/or safety of drugs. Specific focus will be on glucuronidation processes and analgesia. |
