The goal at this stage should be to more strengthen the knowing with the drug properties in vivo and to extrapolate findings, identifying correlations or creating predictions about a drug’s functionality in people . Juvenile toxicological scientific studies, which involve young animals, have already been employed to investigate a drug’s pharmacology and toxicology. Findings are extrapolated assuming a correlation concerning developmental development in animals and young children . Even though the assumptions and rationale can be supported for some indications, many issues really need to be addressed to permit proper interpretation on the findings. In contrast, M&S can optimise the use and interpretation of those data, enabling a mechanism-based, systematic extrapolation on the data across species . Furthermore, it allows quantitative assessment of age- or growth-related differences in drug effects and consequently the potential implications for different paediatric age groups . In addition, the techniques available at this stage, such as PBPK and PBPK-PD models , can use in vitro data to ROCK inhibitor kinase inhibitor predict plasma and tissue concentrations . This implies substantial reduction in the number of animals per experiment and sometimes the replacement of animals by in silico experiments. Also in this case, the use of a model-based approach allows optimisation of experimental protocols, improving the accuracy and efficiency of data extrapolation. In summary, the benefits from M&S methodologies at the non-clinical stage include the prediction and characterisation of primary PK parameters and pharmacodynamic properties . Model parameters can then be employed to predict the dose range to become tested in clinical research, including the requirements for optimal sampling buy MDV3100 selleck chemicals and study design . M&S in clinical drug development Limited availability of patients and practical constraints, such as difficulties in blood sampling, have often been made use of as justification for the lack of systematic evaluation of drug response in youngsters . M&S can address many of these limitations, but its wide implementation in clinical development has remained wishful thinking. This is partly due to the lack of comprehending and working knowledge in quantitative pharmacology and pharmacometrics by spon- sors, regulatory agencies and investigators who are responsible for the planning, design and/or approval of clinical trials. PBPK and disease models The difficulties in performing paediatric trials constrain physicians in extrapolating data from the adult population to little ones. For this purpose, simple allometric methods based on body weight or body surface area are already frequently utilised. However, particularly in neonates and infants, the use in the allometric approach may fail to identify the ideal dosing range .