Cross clinical-experimental-computational qualification of in silico drug trials on human cardiac purkinje cells for proarrhythmia risk prediction

ABSTRACT: The preclinical identification of drug-induced cardiotoxicity and its translation into human risk are still major challenges in pharmaceutical drug discovery. The ICH S7B Guideline and Q&A on Clinical and Nonclinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential promotes human in silico drug trials as a novel tool for proarrhythmia risk assessment. To facilitate the use of in silico data in regulatory submissions, explanatory control compounds should be tested and documented to demonstrate consistency between predictions and the historic validation data. This study aims to quantify drug-induced electrophysiological effects on in silico cardiac human Purkinje cells, to compare them with existing in vitro rabbit data, and to assess their accuracy for clinical pro-arr

SUBMITTER: Trovato C 

PROVIDER: S-EPMC9581132 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature