The Simcyp^® Population-based ADME Simulator

Abstract

The Simcyp^® population-based absorption, distribution, metabolism and excretion simulator is a platform and database for ‘bottom-up’ mechanistic modelling and simulation of the processes of oral absorption, tissue distribution, metabolism and excretion of drugs and drug candidates in healthy and disease populations. It combines experimental data generated routinely during preclinical drug discovery and development from in vitro enzyme and cellular systems and relevant physicochemical attributes of compound and dosage form with demographic, physiological and genetic information on different patient populations. The mechanistic approach implemented in the Simcyp Simulator allows simulation of complex absorption, distribution, metabolism and excretion outcomes, particularly those involving multiple drug interactions, parent drug and metabolite profiles and time- and dose-dependent phenomena such as auto-induction and auto-inhibition. This review describes the framework and organisation of the simulator and how it combines the different categories of information.

Keywords::

• ADME
• in vitro–in vivo extrapolation
• modelling and simulation
• physiologically-based pharmacokinetic models
• population-based pharmacokinetic modelling
• Simcyp^®

Acknowledgements

The authors thank the rest of the Simcyp team for their contributions to the development of the Simulator. We also appreciate the continued support of the Simcyp consortium members.

Notes