Cardiac

Abstract

This chapter highlights various non-automated classical in vitro techniques used today to evaluate drug effects on cardiac electrophysiology. It then outlines a three-pronged preclinical initiative called the Comprehensive In Vitro Proarrhythmia Assay (CiPA), which consists of understanding the effects of new molecular entities on multiple ion channels (including IKr) using voltage clamp techniques, in silico prediction simulations (proarrhythmic liability) based on the ion channel effects, and an integrated human cellular study to provide confirmatory electrophysiological data (most likely involving human stem cell-derived cardiomyocytes (CMs)). The chapter also discusses extremely valuable technology for safety pharmacologists, different between in vitro and in vivo models that can help to identify drugs with potential negative and positive effects on cardiac contractility and how the CV SP assessment of conventional small molecules differs from the approach taken for biologics. Finally the chapter discusses why safety pharmacologists should consider embracing new approaches