Pharmacokinetics and electrophysiological effects of sotalol hydrochloride in horses.

This research studied the effect of the drug sotalol on horses, considering its potential to treat arrhythmias. The researchers examined the effectiveness of different dosages and their influence on various electro- and echocardiographic measures.

Objective and Methodology

The goal of the research was to understand the pharmacokinetics—the actions of a drug within the body—and effects of sotalol hydrochloride, particularly at varying oral dosages, on horses. The study aimed to determine how this drug influenced electro- and echocardiographic measures, as well as the monophasic action potential (MAP) and effective refractory period (ERP) of the right atrial and ventricular regions of the heart.

• The experiment followed a double-blind, placebo-controlled process involving six unfasted Warmblood horses.
• These horses received varying doses (0, 2, 3, or 4 mg/kg bodyweight) of sotalol orally, twice a day for nine consecutive days. This was a randomised cross-over design, meaning the drug was administered to each horse at different sequences.
• Echocardiography, surface electrocardiography and the determination of sotalol plasma concentrations, as well as right atrial and right ventricular MAPs and ERPs, were performed under steady-state conditions.

Results

Using nonlinear mixed-effect modelling, mean steady-state plasma concentrations of sotalol for varying dosages were obtained and used to understand the distribution and elimination of the drug in the horses’ bodies.

• The researchers found that sotalol significantly increased the QT interval (the time taken for the heart to go through electrical depolarisation and repolarisation cycles) and ERPs.
• Surprisingly, increasing dosages did not result in a corresponding increase in QT intervals or ERPs, implying a saturation effect at higher dosages.
• No significant changes were noted in echocardiographic measures and other electrocardiographic measures, and MAP durations at 90% repolarisation were not significantly different during sotalol treatment.
• Aside from transient local sweating, the horses showed no side effects.

Conclusions

The researchers concluded that sotalol, at all studied doses, increased the QT interval and ERP. This suggests that the drug may be an effective long-term anti-arrhythmic therapy for horses. Despite the promising results, the researchers acknowledged potential limitations due to the study’s small size; factors such as the feeding of hay might have impacted the drug’s pharmacokinetics.