抄録
Physiological sensitivity of canine telemetry assay to detect MK-499 induced QT prolongation was compared with those of the following models: pentobarbital-anesthesia (Pento), pentobarbital- anesthesia and vagotomy (Pento+V), isoflurane-anesthesia (Iso) and isoflurane-anesthesia and vagotomy (Iso+V). Telemetry assay was conducted with latin’s square cross-over design in four beagles while the anesthetized assay was performed by cumulative infusion. The magnitudes of the QT prolongation at higher exposure levels ( >5 ng/mL) were as follow: telemetry assay < Pento = Pento+V < Iso = Iso+V, but the concentration of MK-499 that induce 5 to 10% of QT prolongation in the telemetry study was equal to the anesthetized models. These results suggest that telemetry assay is equivalent to the anesthetized models for detecting minimum changes in QT interval of novel compound.
