抄録
The QT interval is commonly used as a surrogate biomarker to predict the risk of developing a potentially fatal ventricular arrhythmia, known as Torsades de Pointes (TdP). However, since the QT interval and heart rate (HR) have an inverse and non-linear relationship, change in HR has to be taken into account when assessing the test substance’s effect on QT interval. ICH S7B recommends that the QT interval data obtained after administration of the test substance should be compared with control and baseline data at similar HR in addition to the QT correction formula. Since the relationship between the QT interval and HR varies among species and between animals within a species, it is critical to know each individual’s normal baseline QT intervals over wide range of HR prior to test substance administration. A retrospective analysis of data generated between August 2003 and August 2005 was performed to show normal physiological range of the QT interval and HR in 3 different species: Dogs (most commonly used in safety pharmacology studies), nonhuman primate (more appropriate species in case of metabolic profiles of the drug), and minipigs (similar cardiovascular physiological characteristics as humans). The QT intervals were collected through the telemetry device in dogs and nonhuman primates, and 6 lead electrocardiographic tracing in minipigs. The main findings in dogs were the relationship between QT interval and HR are different depends on the source of the animals.
