In vitro-in vivo extrapolation of drug-induced proarrhythmia predictions at the population level

Drug cardiotoxicity is a serious issue for patients, regulators, pharmaceutical companies and health service payers because they are all affected by its consequences. Despite the wide range of data they generate, existing approaches for cardiac safety testing might not be adequate and sufficiently cost-effective, probably as a result of the complexity of the problem. For this reason, translational tools (based on biophysically detailed, mathematical models) allowing for in vitro-in vivo extrapolation are gaining increasing interest. This current review describes approaches that can be used for cardiac safety assessment at the population level, by accounting for various sources of variability including kinetics of the compound of interest.