Combining an in silico proarrhythmic risk assay with a tPKPD model to predict QTc interval prolongation in the anesthetized guinea pig assay.

ABSTRACT: Human-based in silico models are emerging as important tools to study the effects of integrating inward and outward ion channel currents to predict clinical proarrhythmic risk. The aims of this study were 2-fold: 1) Evaluate the capacity of an in silico model to predict QTc interval prolongation in the in vivo anesthetized cardiovascular guinea pig (CVGP) assay for new chemical entities (NCEs) and; 2) Determine if a translational pharmacokinetic/pharmacodynamic (tPKPD) model can improve the predictive capacity. In silico simulations for NCEs were performed using a population of human ventricular action potential (AP) models. PatchXpress® (PX) or high throughput screening (HTS) ion channel data from respectively n = 73 and n = 51 NCEs were used as inputs for the in silico population. These

SUBMITTER: Morissette P 

PROVIDER: S-EPMC7322544 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature