Description

Notably, PBPK models are based on a large amount of prior anatomical and physiological information ranging from the organism level to the cellular scale. PBPK models can also be used to analyse dose-related events. This approach has recently been used for model-based risk assessment of statin-induced myopathy. Advances in multi-physics cardiac models now allow complex interactions between cardiac mechanics, electrophysiology and metabolism to be simulated within a common computational framework. The ability of these models to quantitatively and biophysically link changes in function of individual proteins to the capacity of the heart to pump blood provides an opportunity to interpret molecular toxicology in the context of physiological and clinically relevant organ scale function. Prior models of the effects of cardiac drug toxicology have focused on arrhythmias, often by replicating animal experiments in silico or re-interpreting drug effects measured in animals in human cell models. These models have had some initial success, however, they are limited by two critical factors. Firstly, although some toxicology affects are the same across species inconsistencies in toxicology between species are a significant factor in characterising pharmacologic risk and are not accounted for. Secondly, none of these models link drug affects to whole organ cardiac function.