Predicting QTc Prolongation in Man From Only In Vitro Data

Mishra et al.(1) in their article "Interaction between domperidone and ketoconazole: toward prediction of consequent QTc prolongation using purely in vitro information" describe the use of physiologically based pharmacokinetic (PBPK) modeling and pharmacodynamic models of cardiac repolarization to predict clinical data from preclinical data. Eliminating the risk of cardiac arrhythmias through delayed repolarization often relies on preclinical data during compound selection. Although there are some limitations, there appears to be significant promise in using this modeling approach.