The aim of this type of study is, to examine the effects of the test item on cardiovascular parameters in telemetered, freely moving conscious animals.
In dogs or minipigs
This in vitro electrophysiology study is designed to gain information concerning the effect of a test item on action potential duration and/or cardiac ionic currents. The human ether-a-go-go related gene (hERG) encodes the inward rectifying voltage gated potassium channel in the heart (IKr). The most common mechanism of QT interval prolongation by pharmaceuticals is inhibition of this channel.
Reduced function of hERG channel lengthens ventricular action potentials, prolongs the QT interval in an electrocardiogram, and increases the risk for potentially fatal ventricular arrhythmias.
This inhibition potential of a test item should be determined early in the drug development.
One of the hERG tests is an in vitro patch-clamp assay where mammalian cell lines stably expressing hERG channel gene are used.
The test item can be evaluated from 1 to 5 concentrations. The dose-response curve and IC50 value are generated after a limit test. Positive control is tested to ensure the sensitivity of the test system.