Analysis of torsadogenic and pharmacokinetic profile of E-4031 in dogs bridging the gap of information between in vitro proarrhythmia assay and clinical observation in human subjects

• Main Authors: Ai Goto (Author), Hiroko Izumi-Nakaseko (Author), Mihoko Hagiwara-Nagasawa (Author), Koki Chiba (Author), Kentaro Ando (Author), Atsuhiko T. Naito (Author), Atsushi Sugiyama (Author)
• Format: Book
• Published: Elsevier, 2018-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

We analyzed torsadogenic and pharmacokinetic profile of E-4031 using chronic atrioventricular block dogs. E-4031 in intravenous doses of 0.03, 0.1 and 0.3 mg/kg over 10 min prolonged QT/QTc, and increased short-term variability of QT in a dose-related manner (n = 4), resulting in onset of torsade de...