Comparison of Electrocardiographic Biomarkers for Differentiating Drug-Induced Single vs. Multiple Cardiac Ion Channel Block.

ABSTRACT: Since introduction of the International Conference on Harmonization proarrhythmia guidelines in 2005, no new marketed drugs have been associated with unacceptable risk of Torsade de Pointes. Although cardiac safety improved, these guidelines had the unintended consequence of eliminating potentially beneficial drugs from pipelines early in development. More recently, it has been shown that a corrected QT (QTc) prolonging drug may be safe if it impacts multiple ion channels vs. only human ether-a-go-go related gene (hERG) and that this effect can be discriminated using QT subintervals. We compared the predictive power of four electrocardiogram (ECG) repolarization metrics to discriminate single vs. multichannel block: (i) traditional 10-second signal averaged triplicates, and (ii) three metr

SUBMITTER: Brockway M 

PROVIDER: S-EPMC6510380 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature