Minimal physiologically-based pharmacokinetic (mPBPK) models are frequently used to model plasma pharmacokinetic (PK) data and utilize and yield physiologically relevant parameters. Compared with classical compartment and whole-body physiologically-based pharmacokinetic modeling approaches, mPBPK models maintain a structure of intermediate physiological complexity that can be adequately informed by plasma PK data. In this tutorial, we present a MATLAB-based tool for the modeling and simulation of mPBPK models (ATLAS mPBPK) of small and large molecules. This tool enables the users to perform the following: (i) PK data visualization, (ii) simulation, (iii) parameter optimization, and (iv) local sensitivity analysis of mPBPK models in a simple and efficient manner. In addition to the theoretical background and implementation of the different tool functionalities, this tutorial includes simulation and sensitivity analysis showcases of small and large molecules with and without target-mediated drug disposition.
© 2019 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.