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.
J Pharmacol Sci
; 137(2): 237-240, 2018 Jun.
Article
em En
| MEDLINE
| ID: mdl-29980434
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperidinas
/
Piridinas
/
Torsades de Pointes
/
Eletrocardiografia
/
Bloqueio Atrioventricular
/
Antiarrítmicos
Tipo de estudo:
Etiology_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Pharmacol Sci
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão