Building in-house PBPK modelling tools for oral drug administration from literature information.

The interest in using physiologically-based pharmacokinetic (PBPK) models as a support to the drug development decision making process has rapidly increased in the last years. These kind of models are examples of the "bottom up" modelling strategy, which progressively integrates into a mechanistic framework different information as soon as they become available along the drug development. For this reason PBPK models can be used with different aims, from the early stages of drug development up to the clinical phases. Different software tools are nowadays available. They can be categorized in "designed software" and "open software". The first ones typically include commercial platforms expressly designed to implement PBPK models, in which the model structure is pre-defined, assumptions are generally not explicitly declared and equations are hidden to the user. Even if the software is validated and routinely used in the pharmaceutical industry, sometimes they do not allow working with the flexibility needed to cope with specific applications/tasks. For this reason, some scientists prefer to define and implement their own PBPK tool in "open" software. This paper shows how to build an in-house PBPK tool from species-related physiological information available in the literature and a limited number of drug specific parameters generally made available by the drug development process. It also reports the results of an evaluation exercise that compares simulated plasma concentration-time profiles and related pharmacokinetic (PK) parameters (i.e., AUC, C