Channelpedia

PubMed 26159293


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNK3 , Kir2.3



Title: CiPA: Ongoing testing, future qualification procedures, and pending issues.

Authors: Icilio Cavero, Henry Holzgrefe

Journal, date & volume: J Pharmacol Toxicol Methods, 2015 Jul 6 , 76, 27-37

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/26159293


Abstract
The comprehensive in vitro proarrhythmia assay (CiPA) is a nonclinical, mechanism-based paradigm for assessing drug proarrhythmic liability.The first CiPA assay determines effects on cloned human cardiac ion channels. The second investigates whether the latter study-generated metrics engender proarrhythmic markers on a computationally reconstructed human ventricular action potential. The third evaluates conclusions from, and searches possibly missed effects by in silico analysis, in human stem cell-derived cardiomyocytes (hSC-CMs). CiPA ad hoc Expert-Working Groups have proposed patch clamp protocols for seven cardiac ion channels, a modified O'Hara-Rudy model for in silico analysis, detailed procedures for field (MEA) and action potential (VSD) measurements in hSC-CMs, and 29 reference drugs for CiPA assay testing and validation.CiPA adoption as drug development tool for identifying electrophysiological mechanisms conferring proarrhythmic liability to candidate drugs is a complex, multi-functional task requiring significant time, reflection, and efforts to be fully achieved.