Draft ICH guideline S7B: Guideline on safety pharmacology studies for assessing the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals.

QT PRODACT: in vivo QT assay in the conscious dog for assessing the potential for QT interval prolongation by human pharmaceuticals.

The goal of the present study was to examine the utility of the conscious dog model by assessing the QT-interval-prolonging potential of ten positive compounds that have been reported to induce QT interval prolongation in clinical use and seven negative compounds considered not to have such an effect. Three doses of test compounds or vehicle were administered orally to male beagle dogs (n=4), a...

ICH guideline S2 (R1) - Genotoxicity testing and data interpretation for pharmaceuticals intended for human use

IN VITRO ELECTROPHYSIOLOGY SAFETY STUDIES (hERG)

ICH S7B guideline regulates the in vitro IKr assay in combination with in vivo QT evaluation prior to first-in-human administration. This guideline has been recommended for adoption by the regulatory bodies of 3 regions (Japan, USA and EU). To support compound development through cardiovascular safety assessment, Charles River Preclinical Services, Edinburgh (PCS-EDI) has developed and operates...

Improvement of QT analysis for Evaluating the Proarrhythmic Risk of Drug: The Importance of Spatial and Temporal Dispersion of Repolarization

Cardiac arrhythmias, in particular life-threatening Torsades de Pointes (TdP) are serious adverse effects associated with a number of pharmaceuticals belonging to different classes. It is therefore critical to have reliable biomarkers for assessing this risk during pre-clinical testing of new compounds. Prolongation of cardiac action potential and consequently of the QT interval of the ECG is g...

Prolongation of the QT interval by ketanserin.

In hypertensive patients single doses of ketanserin 40 mg prolonged the corrected QT interval (QTc) for at least 8 hours, with a maximal increase of 35 ms (P less than 0.001, n = 6) after 2 hours. During chronic dosing (20 and 40 mg b.d.) the QTc was further prolonged, by 46 and 45 ms respectively. QTc prolongation after treatment with a mean dose of 73 mg/day for 7 weeks (n = 26) was significa...