Modeling and simulation approach for assessing proarrhythmic potency of the non-cardiological drugs

The study aimed to assess the usefulness of the modeling and simulation approach for the proarrhythmic potency of the non-cardiological drugs prediction. Ability to mimic population effect with use of the virtual population generator on the QTc value was tested. ToxComp version 1.5 (www.tox-comp.net) with ten Tuscher human cardiomyocyte model (1D string -Epi/M/Endo - 20/30/50%) was used to mimic the clinical study and formoterol was chosen as a model drug (Lecaillon study - 8 males/4 females, mean age[SD] - 24[6]). Simulation time was set to 10 seconds and the QTc [ms] value with Fridericia correction was chosen as an endpoint. Obtained simulation results were compared with clinical study outcomes. None of the differences between observed and predicted values were statistically significant (t-test). Current study proves that such phenomena can be predicted with use of the mathematical models working on the population level.