Combination therapy with mexiletine and sotalol suppresses inherited ventricular arrhythmias in German shepherd dogs better than mexiletine or sotalol monotherapy: a randomized cross-over study.
OBJECTIVE
To determine the spontaneous variability of ventricular arrhythmias (VA) and evaluate anti-arrhythmic efficacy of mexiletine, sotalol, and a mexiletine-sotalol combination in German shepherd dogs (GSD) with inherited arrhythmias.


METHODS
12 affected GSD, median age 20 weeks, received mexiletine (8 mg/kg PO q8 h), sotalol (2.5 mg/kg PO q12 h), and combination therapy for 6 days in random order. Pre- and post-treatment 24 h Holter recordings were acquired, allowing determination of VA variability and reduction in 24 h VA for each treatment. Drug concentrations during each arm were measured.


RESULTS
An anti-arrhythmic effect could be inferred if ventricular premature complexes (VPC), ventricular couplets (V(cpl)), ventricular tachycardia runs (VT(runs)) and total ventricular ectopy (VE(tot)) frequency were reduced by 61%, 97%, 98%, and 63% (1 control Holter model), by 53%, 94%, 95%, and 54% (4 control Holter model) and by 54%, 95%, 96% and 56% (3 control Holter model). Combination therapy reduced VPC and VE(tot) in more dogs (5/12 and 6/12) than mexiletine (1/11 and 2/11) or sotalol (2/9 and 1/9) (p < 0.05). The combination therapy reduced the mean number of VPC, V(cpl), and VE(tot). Sotalol monotherapy produced an increase in VT(runs). Plasma mexiletine concentration was higher during combination therapy than with monotherapy.


CONCLUSIONS
Combination therapy reduced VPC in affected GSD. Sotalol monotherapy increased VT(runs). Combination therapy increased plasma mexiletine concentrations.
Gelzer
Anna R M
AR
Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. arg9@cornell.edu
Kraus
Marc S
MS
Rishniw
Mark
M
Hemsley
Shari A
SA
Moïse
N Sydney
NS
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000662:veterinary*; D018592:Cross-Over Studies; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004359:Drug Therapy, Combination / Q000662:veterinary; D015716:Electrocardiography, Ambulatory / Q000662:veterinary; D005260:Female; D008297:Male; D008801:Mexiletine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011446:Prospective Studies; D013015:Sotalol / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000662:veterinary; D018879:Ventricular Premature Complexes / Q000188:drug therapy / Q000662:veterinary
D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D013015:Sotalol