Prediction of Thorough QT study results using action potential simulations based on ion channel screens.

ABSTRACT:

Introduction

Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development.

Methods

Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms - IonWorks Qua

SUBMITTER: Mirams GR 

PROVIDER: S-EPMC4266452 | biostudies-literature | 2014 Nov-Dec

REPOSITORIES: biostudies-literature