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Pharmacokinetics and electrophysiological effects of sotalol hydrochloride in horses
Author(s) -
Broux B.,
De Clercq D.,
Decloedt A.,
Vera L.,
Devreese M.,
Gehring R.,
Croubels S.,
Loon G.
Publication year - 2018
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.1111/evj.12765
Subject(s) - sotalol , electrophysiology , hydrochloride , pharmacology , pharmacokinetics , medicine , anesthesia , chemistry , atrial fibrillation , organic chemistry
Summary Background Arrhythmias in horses may require long‐term anti‐arrhythmic therapy. Unfortunately, oral anti‐arrhythmic drugs for use in horses are currently scarce. In human patients and small animals, sotalol, a β‐blocker with class III anti‐arrhythmic properties, is often used for long‐term treatment. Objectives To determine the pharmacokinetics of sotalol at multiple oral dosages in unfasted horses, as well as the effects on electro‐ and echocardiographic measurements, right atrial and ventricular monophasic action potential ( MAP ) and effective refractory period ( ERP ). Study design Placebo controlled, double‐blinded experiment. Materials and methods Six healthy, unfasted Warmblood horses were given either 0, 2, 3 or 4 mg/kg bodyweight (bwt) sotalol orally ( PO ) twice daily (bid) for 9 days in a randomised cross‐over design. Echocardiography and surface electrocardiography were performed and plasma concentrations of sotalol and right atrial and right ventricular MAP s and ERP s were determined at steady‐state conditions. Statistical analysis was performed using a repeated measures univariate analysis with post hoc Bonferroni corrections. Results Calculated mean steady‐state plasma concentrations determined by nonlinear mixed‐effect modelling were 287 (range 234–339), 409 (359–458) and 543 (439–646) ng/mL for 2, 3 and 4 mg/kg bwt sotalol PO bid respectively. Sotalol significantly increased the QT interval and ERP s, but, despite increasing plasma concentrations, higher dosages did not result in a progressive increase in QT interval or ERP s. Echocardiographic and other electrocardiographic measurements did not change significantly. MAP durations at 90% repolarisation were not significantly different during sotalol treatment. Besides transient local sweating, no side effects were noted. Main limitations Study size and ad libitum feeding of hay. Conclusions Sotalol at a dose of 2, 3 and 4 mg/kg bwt PO bid increases the QT interval and ERP and might be a useful drug for long‐term anti‐arrhythmic therapy in horses.