Mathematical Modelling of Physiologically-Based Pharmacokinetics

Lead Research Organisation: University of Strathclyde
Department Name: Mathematics and Statistics

Abstract

The main focus of this 4 year PhD proposal will be to develop advanced PBPK mathematical models and, in particular, to understand the translation of models between species to support systems biology based approaches and improve biological predictability across species.

The project will provide foundational knowledge for the development of predictive mathematical models and integrates current knowledge regarding bio-analytical approaches used in medicines development with computational analysis. As such it offers a multidisciplinary training opportunity for the student, which will include the following key stages:

Stage 1 (months 0-6): SMSTC training and, if necessary, relevant classes from the Strathclyde Institute of Pharmacy and Biomedical Sciences.

Stage 2 (months 7-18): Review mathematical models of PBPK which will including organ specific models (i.e. gut, liver, kidney, brain) as well as models to predict selected inputs including plasma protein binding, tissue:plasma partition coefficients and tissue protein binding values. Implement simple PBPK model and supports systems pathway predictions of selected targets/compounds and compare with published predictions for different species.

Stage 3 (months 19-31): Implement a more detailed mathematical model (i.e. including of relatively simple models of fluid flow, absorption, fluid-tissue interaction) for the gut and compare with ACAT/ADAM [Huang 2009]. Consider the translation of models between species using appropriate scaling and addition/removal of relevant/irrelevant physical processes within the model.

Stage 4 (months 32-40): Extend the methodology of model translation between species to other organs. Consider target concentration/effect relationships for specific compounds (specified by GSK) and compare to external databases.

Stage 5 (months 40-44) Consider a whole body translational methodology, grouping organs into those where translation can be thought of as allometric and those where additional physiological effects are needed.

Stage 6 (months 44-48) Write up thesis and a related industry report that may contain confidential information.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509371/1 01/10/2015 30/09/2020
1694052 Studentship EP/N509371/1 01/10/2015 30/09/2019 John McGowan