Roberto Padrini, Mohammad Al Bunni*, Monica Mollichelli*, Antonella Alberti**, Roberto Varotto**, Pietro Maiolino*, Mariano Ferrari**.
Department of Pharmacology and Anesthesiology and
**Department of Clinical and Experimental Medicine, University of Padova, *Division of Cardiology, Cittadella Hospital, Cittadella, Italy
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BACKGROUND. Rac-sotalol prolongs cardiac
action potential duration and QT interval (mostly at low heart rates) and these changes
can trigger polymorphic ventricular tachycardia. This study was planned to evaluate in
man whether mexiletine, at therapeutic doses, can antagonize sotalol-induced QT
prolongation.
METHODS. The electrocardiographic interaction between sotalol and mexiletine was
studied in patients with arrhythmias potentially responsive to sotalol treatment. Heart
rate/QT relationship was experimentally assessed in each patient, in order to
individually correct the QT interval by heart rate. Then, patients received in random
sequence, 160 mg sotalol (po) and (48 h later) 160 mg sotalol (po)+400 mg mexiletine
(po). ECGs were recorded and plasma drug concentrations were assayed at proper
times after drug administration and the logarithm of sotalol plasma concentration was
correlated with the corresponding per cent change in QT interval duration. The
regression lines obtained for each patient in the absence and in the presence of
mexiletine were compared in terms of Y-intercept and slope.
RESULTS. At present the study has been completed in 5 patients (20 were planned). In
one patient sotalol did not induce significant QT changes. In two cases mexiletine
administration resulted in a significant rightward displacement of the log
concentration-effect relationship, while in the last two patients no significant shift was
observed. The two patients who responded to mexiletine had also had the greatest
QT prolongation following sotalol administration.
CONCLUSIONS. These preliminary data suggest that mexiletine-sotalol antagonism is
related to sotalol QT effect.
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