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Pharmacokinetics and Electrophysiological Effects of Sotalol Hydrochloride in Horses

Pharmacokinetics and Electrophysiological Effects of Sotalol Hydrochloride in Horses

B Broux, D De Clercq, A Decloedt, L Vera, M Devreese, R Gehring, S Croubels, G van Loon

Equine Vet J. 2018 May;50(3):377-383.

PMID: 29023952

Abstract:

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 MAPs and ERPs 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 ERPs, but, despite increasing plasma concentrations, higher dosages did not result in a progressive increase in QT interval or ERPs. 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP959240-B	(±)-Sotalol hydrochloride		959-24-0	Price

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