| Autor: |
Ai Goto, Hiroko Izumi-Nakaseko, Mihoko Hagiwara-Nagasawa, Koki Chiba, Kentaro Ando, Atsuhiko T. Naito, Atsushi Sugiyama |
| Jazyk: |
angličtina |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
Journal of Pharmacological Sciences, Vol 137, Iss 2, Pp 237-240 (2018) |
| Druh dokumentu: |
article |
| ISSN: |
1347-8613 |
| DOI: |
10.1016/j.jphs.2018.06.005 |
| Popis: |
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 pointes in 1 animal after the middle dose and 4 animals after the high dose, while it attained peak plasma concentrations of 16.5, 60.5 and 182.5 ng/mL at 10 min after their start of administration, respectively (n = 2). These results bridge the gap of information between in vitro proarrhythmia assay and clinical observation in human subjects. Keywords: E-4031, Torsade de pointes, CiPA |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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