The identification of the gaps in data knowledge on the safe and effective prescription of drugs in children. Demonstration that studies with a pediatric adapted design are feasible to do, taking in account the specific pediatric characteristics such as size-dependency, age related maturation differences, specific pathophysiology and ontogenesis of the diseases, and the high incidence of comorbidities, including PK/PD data during size dependent dosing studies. To respond to the need to do pediatric studies in children with comorbidity, critical ill children or neonates, (since extrapolating PK/PD data and dose regimens from, adults and even young children with a monosymptomatic disease is simply not possible) and to understand the mechanisms involved in the differences. To develop a tool such as surrogate parameters that can be used in monitoring and titrating the individual patient. To find a strategy that might prevent off label use of a drug. To optimize existing dose regimens by additional PK/PD studies. To develop a juvenile animal model allowing to obtain essential information on PK/PD from the neonatal period into adolescence, information to be extrapolated to the growing and maturating child. This model offers also the advantage of studying long efficacy and side-effects. To create and fine-tune the pharmacological modelling tool, to predict PK/PD characteristics of a drug in children. To evaluate and reformulate ethical standards.
Our project has been subdivided into 8 work packages. WP1 – Systematic literature review and retrospective studies aiming at describing off-label use of drugs in current daily paediatric practice. WP2 – Prove with ‘real live cases’ (lisinopril, desmopressin, ciprofloxacin) that pediatric clinical trials are feasible to do. WP3 – Development of a juvenile animal model (pig) for pharmacokinetic research with the real live cases mentioned in WP2. WP4 – Physiology based pharmacokinetic modeling(PB- PK) which integrates data of WP2 and WP3. WP5 – Investigation of co-morbidity and critical illness on pharmacokinetics and pharmacodynamics in children who are admitted to the Pediatric Intensive Care Unit (PICU). WP6 – Investigation of influence of premature renal function on drug elimination and on long term nephrotoxicity. WP7 – Formulation of guidelines and recommendation for future pediatric clinical trials by evaluation of our project results. WP8 – Investigation of moral, ethical and legal aspects of pediatric drug studies.