2. Academic Validation
  3. Possibility as an anti-cancer drug of astemizole: Evaluation of arrhythmogenicity by the chronic atrioventricular block canine model

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

  • J Pharmacol Sci. 2016 Jun;131(2):150-3. doi: 10.1016/j.jphs.2016.04.024.
Hiroko Izumi-Nakaseko 1,  Yuji Nakamura 1,  Xin Cao 1,  Takeshi Wada 1,  Kentaro Ando 1,  Atsushi Sugiyama 2
Affiliations

Affiliations

  • 1 Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan.
  • 2 Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143-8540, Japan. Electronic address: atsushi.sugiyama@med.toho-u.ac.jp.
PMID: 27262902 DOI: 10.1016/j.jphs.2016.04.024
Abstract

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.

Keywords

Astemizole; Re-profiling; Torsade de pointes.

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