Cardiac safety issue


Meetings / Conferences Meet us at the IBC Drug Discovery and Development Conference Aug 4-7. Buzz Brown to speak Aug 6 at 10:10AM Ion Channels Play Key Role in R&D Genetic Enginering News article (Jun 1 2008 (Vol. 28, No. 11)). ChanTest profiled. Spotlight Paper Alfuzosin delays cardiac repolarization by a novel mechanism (2008) J Pharmacol Exp Ther. 324(2):427-433

Preclinical Cardiac Risk Assessment:
QT Prolongation (long QT) from nonantiarrhythmic drugs (“nards”)

Regulatory bodies in the US, Canada, Europe and Japan, through the International Conference on Harmonisation (ICH), recommend in vitro preclinical tests to evaluate investigational drugs for their potential to impair cardiac repolarization and prolong the QT interval of the ECG. ICH guideline S7B specifies that a GLP hERG study be included with each IND submission. A positive preclinical signal from a non-antiarrhythmic drug (“nard”) requires that a thorough clinical trial be performed according to the ICH E14 guidance. Learn more about these regulatory considerations.

A serious complication associated with impaired cardiac repolarization and QT prolongation is an increased risk of potentially fatal Torsades de Pointes. Thus far, these events have been linked mainly, but not exclusively, to a block of hERG – the cardiac ion channel responsible for the rapid repolarizing potassium current: IKr.

A 10 ms increase in rate-corrected QT interval (QTc) may indicate risk of Torsades de Pointes (TdP).
Incidence of TdP is too low to be detected in clinical trials. More than 40 marketed drugs have been associated with hERG channel block, QT prolongation, and TdP. ChanTest’s cardiac action potential (APD) assay in Purkinje fibers and isolated heart QT prolongation (CT-QT) assay can help determine risk.

Preclinical Cardiac Risk Assessment: QT Prolongation (long QT) from nonantiarrhythmic drugs (“nards”)

Preclinical Cardiac Risk Assessment:
QT Prolongation (long QT) from nonantiarrhythmic drugs (“nards”)