Increased susceptibility for atrial and ventricular cardiac arrhythmias in mice treated with a single high dose of ibrutinib

Publication date: Available online 7 December 2017 Source:Canadian Journal of Cardiology Author(s): Jari M. Tuomi, Anargyros Xenocostas, Douglas L. Jones Atrial Fibrillation (AF) is a side-effect of ibrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase used for treatment of B-cell lymphoproliferative disorders. We determined if single (2 or 10 mg/kg), or chronic (14 day) oral ibrutinib followed by 24 hour washout conferred susceptibility to electrically-induced arrhythmias in 1-mo male C57BL/6 mice. A single higher dose of ibrutinib increased arrhythmia inducibility. There was no inducibility difference after chronic dosing with washout. This suggests that high serum drug levels may be responsible for the pro-arrhythmic effect of ibrutinib and that an altered dosing strategy may mitigate the side effects. Teaser We determined if a single or 14 day ibrutinib administration of ibrutinib with 24 hour washout conferred susceptibility to electrically-induced arrhythmias in the mouse. Single oral ibrutinib conferred electrically-induced arrhythmia while repeated 14 daily oral ibrutinib with 24 hour washout did not enhance electrical pacing-induced arrhythmia in the mouse. Thus acute arrhythmia may be due to high serum ibrutinib levels.
Source: Canadian Journal of Cardiology - Category: Cardiology Source Type: research