Possibility as an anti-cancer drug of astemizole: Evaluation of arrhythmogenicity by the chronic atrioventricular block canine model

• Main Authors: Hiroko Izumi-Nakaseko, Yuji Nakamura, Xin Cao, Takeshi Wada, Kentaro Ando, Atsushi Sugiyama
• Format: Article
• Language: English
• Published: Elsevier 2016-06-01
• Series: Journal of Pharmacological Sciences
• Subjects: Astemizole; Re-profiling; Torsade de pointes
• Online Access: http://www.sciencedirect.com/science/article/pii/S1347861316300524

Since astemizole in an oral dose of 50 mg/kg/day was recently reported to exert anti-cancer effect in mice, we evaluated its proarrhythmic potential using the atrioventricular block dogs in order to clarify its cardiac safety profile. An oral dose of 3 mg/kg prolonged the QT interval without affecting the QTc (n = 4), whereas that of 30 mg/kg increased the short-term variability of repolarization and induced premature ventricular contractions in each animal, resulting in the onset of torsade de pointes in 1 animal (n = 4). Thus, proarrhythmic dose of astemizole would be lower than anti-cancer one, limiting its re-profiling as an anti-cancer drug.