Towards Mechanistic Characterization of Inflamatory Bowel Diseases and Complicated Urinary Tract Infection using Systems Pharmacology Approach

Abstract

Pharmacometrics and Systems Pharmacology (PSP) is a constant evolving science that is being forced to deal with new challenges. The need to develop multi-scale models using data from different sources and the integration of different modelling strategies to create more mechanistic models is essential to answer the unmet research and clinical related questions. This thesis constitutes an effort of learning and application of a broad spectrum of modelling techniques and tools to mechanistically characterize two complex diseases: Inflammatory Bowel Disease and complicated Urinary Tract infection. Over the different chapters, we provide alternatives to overcome data limitation to build and validate a variety of PSP models able to reproduce different systems to be applied to both drug development and clinical care. The resulting models and repositories are also provided together with the main considerations for further improvement. We believe that this thesis proves that Systems pharmacology could reduce the late-stage attrition in the drug development process, but also could drive optimal intervention strategies resulting from the combination of individual physiological information and computational methodologies.