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Pharmacokinetics and electrophysiological effects of sotalol hydrochloride in horses

Barbara Broux UGent, Dominique De Clercq UGent, Annelies Decloedt UGent, Lisse Vera UGent, Mathias Devreese UGent, R Gehring, Siska Croubels UGent and Gunther van Loon UGent (2018) EQUINE VETERINARY JOURNAL. 50(3). p.377-383
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 -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.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
horse, arrhythmia, anti-arrhythmic drugs, monophasic action potential, refractory period, INDUCED ATRIAL-FIBRILLATION, QUINIDINE, ECHOCARDIOGRAPHY, FLECAINIDE, MANAGEMENT, SAFETY, DRUGS
journal title
EQUINE VETERINARY JOURNAL
Equine Vet. J.
volume
50
issue
3
pages
377 - 383
Web of Science type
Article
Web of Science id
000429541500015
ISSN
0425-1644
DOI
10.1111/evj.12765
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
8544859
handle
http://hdl.handle.net/1854/LU-8544859
date created
2018-01-14 22:28:40
date last changed
2018-05-18 13:57:49
@article{8544859,
  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 -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.},
  author       = {Broux, Barbara and De Clercq, Dominique and Decloedt, Annelies and Vera, Lisse and Devreese, Mathias and Gehring, R and Croubels, Siska and van Loon, Gunther},
  issn         = {0425-1644},
  journal      = {EQUINE VETERINARY JOURNAL},
  keyword      = {horse,arrhythmia,anti-arrhythmic drugs,monophasic action potential,refractory period,INDUCED ATRIAL-FIBRILLATION,QUINIDINE,ECHOCARDIOGRAPHY,FLECAINIDE,MANAGEMENT,SAFETY,DRUGS},
  language     = {eng},
  number       = {3},
  pages        = {377--383},
  title        = {Pharmacokinetics and electrophysiological effects of sotalol hydrochloride in horses},
  url          = {http://dx.doi.org/10.1111/evj.12765},
  volume       = {50},
  year         = {2018},
}

Chicago
Broux, Barbara, Dominique De Clercq, Annelies Decloedt, Lisse Vera, Mathias Devreese, R Gehring, Siska Croubels, and Gunther van Loon. 2018. “Pharmacokinetics and Electrophysiological Effects of Sotalol Hydrochloride in Horses.” Equine Veterinary Journal 50 (3): 377–383.
APA
Broux, Barbara, De Clercq, D., Decloedt, A., Vera, L., Devreese, M., Gehring, R., Croubels, S., et al. (2018). Pharmacokinetics and electrophysiological effects of sotalol hydrochloride in horses. EQUINE VETERINARY JOURNAL, 50(3), 377–383.
Vancouver
1.
Broux B, De Clercq D, Decloedt A, Vera L, Devreese M, Gehring R, et al. Pharmacokinetics and electrophysiological effects of sotalol hydrochloride in horses. EQUINE VETERINARY JOURNAL. 2018;50(3):377–83.
MLA
Broux, Barbara, Dominique De Clercq, Annelies Decloedt, et al. “Pharmacokinetics and Electrophysiological Effects of Sotalol Hydrochloride in Horses.” EQUINE VETERINARY JOURNAL 50.3 (2018): 377–383. Print.