Validating cardiac ion channels using automated electrophysiology for the CiPA paradigm
Haiyang (David) Wei, PhD
Eurofins Pharma Discovery Services
Drug-induced QT interval prolongation and Torsades de Pointes (TdP) arrhythmia are the leading causes for drug withdrawal from the market. For the past decade, in vitro hERG channel assays and in vivo QT measurements have been conducted as surrogates for proarrhythmic risk propensity according to ICH S7B and ICH E14 guidelines. This paradigm, although effective, suffered from lack of specificity and led to unnecessary compound attrition during drug development. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) is a new cardiac safety testing paradigm intended to address this limitation with improved prediction of drug’s proarrhythmic liability. This new paradigm includes a panel of in vitro assays that integrates effects of the test compounds on several cardiac ion channels.
In this study, three cardiac ionic currents (IKr, ICa, INa, fast) were validated on a novel microfluidic-based automated patch clamp system to evaluate accuracy, precision and robustness of the assays. The results demonstrate suitability of the system for high throughput screening of drug effects on cardiac ionic currents, and provide data for in silico reconstructions in the CiPA paradigm for defining proarrhythmic risk.
- Learn about the in vitro assay panel on cardiac ion channels relating to the CiPA paradigm
- Learn about the application of automated patch clamp in assessing cardiac ionic currents