Work package 5: Pharmacokinetic & Modelling and Simulation
Description of the work package
An a priori application of modelling and simulation techniques will be performed in this work package to optimize the paediatric trial designs, select the appropriate dose level and dosing regimens to be studied, and to develop sampling schemes. This effort will be based on various extrapolation approaches that incorporate physiological and pathophysiological data, pharmacokinetic and pharmacodynamics data from preclinical studies, in vitro experiments, and adult and paediatric data from pilot studies. When pharmacokinetic data from the Bioavailability and Food Effect in Healthy Adults are available, the models will be refined as needed.
The simulations will visualize trial designs, dosing regiments, and sampling schemes for discussion with the other project partners. An a posteriori application of modelling and simulation techniques to the data from the paediatric studies will also be performed to refine the models and to learn more about the underlying developmental pharmacology of enalapril and enalaprilat. Classical compartmental pharmacokinetic and pharmacokinetic /pharmacodynamics techniques as well as physiologically based modelling and simulation techniques and population-based approaches will be applied to derive maximum information from the limited data collected in paediatric studies and to establish a consistent framework that allows the exploration of model-based dosing recommendations (see image below).