抄録
Telemetry study is recommended for evaluating the QT liability of drugs. For establishment of telemetry study, it is important to select appropriate QT/RR correction formulas and confirm the QT prolongation induced by positive compounds. We had already reported that Bazett’s and Fridericia’s formulas are suitable for correcting QT interval against RR interval in miniature swine (JST, P-20, 2005). In this study, we examined the effect of E-4031, selective Ikr channel blocker, on the cardiovascular system including QT interval in order to explain the utility of miniature swine telemetry study for predicting drug-induced QT prolongation.Göttingen miniature swine was obtained from Chugai Research Institute for Medical Science Inc. (male, 4 animals/ group). ECG parameters (PR, QRS, QT intervals and QTc corrected by Bazett’s and Fridericia’s formulas), heart rate and blood pressure were recorded in conscious and unrestrained condition by telemetry system (OPEN ART & HEM). The animals were given intravenous injection of E-4031 at 0.004, 0.02 and 0.1 mg/kg. E-4031 prolonged QT interval and QTc (QTcB or QTcF) in a dose-dependent manner and decreased heart rate at 0.02 and 0.1 mg/kg. In contrast, E-4031 had no effects on blood pressure, PR and QRS intervals at any doses tested. From the result that Ikr channel blockade prolong QTc on miniature swine, it is concluded that telemetry miniature swine is available for evaluating QT-prolonging risk of drug.
