Amiodarone is a benzofuran-derived drug that was developed more than 35 years ago for management of myocardial ischemia in humans.1 Although the antiarrhythmic and preventative effects of amiodarone on atrial flutter and AF have been known since the early 1980s, the drug has been used most extensively for treatment of ventricular arrhythmias.2 Because of its potency as an antiarrhythmic drug, amiodarone is receiving renewed attention for potential use in treatment and prevention of AF.3
Amiodarone has high lipid solubility and is taken up extensively by tissues, resulting in a high volume of distribution and prolonged elimination t1/2. Estimates of elimination t1/2 vary, depending on study design and sensitivity of the analytic methods used.3,4 A model for estimating pharmacokinetic variables of amiodarone in ponies has been described.5 As is true in humans, AF is one of the most common cardiac arrhythmias in horses.6,7 The chief clinical sign in horses is exercise intolerance. The prognosis for return to normal sinus rhythm is influenced by the duration for which the arrhythmia has persisted and by atrial diameter; duration of the arrhythmia for longer than 6 months or development of the arrhythmia in association with atrial dilatation is associated with a poor prognosis for successful cardioversion. Atrial dilatation can be caused by mitral valve regurgitation7,8 and can also result from AF. In many horses with AFa, no underlying cardiac disease is detected and treatment is often successful. After cardioversion, horses generally return to the previous level of athletic ability.7
The standard treatment for AF is administration of QS, although up to 76% of treated horses develop 1 or more adverse effects, including urticaria, nasal mucosal edema, colic, diarrhea, laminitis, tachycardia, anaphylactic shock, syncope, or sudden death.7–12 In some countries, QS has become difficult to obtain and will likely become more expensive.13 These factors have stimulated the search for an alternative and less toxic drug for treatment of chronic AF in horses.
Multiple antiarrhythmic drugs are used for treatment of AF in humans,14 some of which have already been investigated for use in horses. Intravenously administered flecainide (a class IC antiarrhythmia drug) and amiodarone (a class III antiarrhythmia drug) have been used for treatment of horses with AF.15,16 The use of flecainide in horses appeared promising for treatment of acute AF in 1 study,17 but it was not useful in horses with chronic AF because of elicitation of ventricular dysrhythmias.15 In another study,16 4 of 6 horses were converted to sinus rhythm after IV administration of amiodarone. In that study, horses received 5 mg of amiodarone/kg per hour for 1 hour followed by 0.83 mg/kg/h for 23 hours and 1.9 mg/kg/h for 30 hours. Infusion was discontinued when conversion was achieved or when adverse effects were observed.16 Because amiodarone appeared to be potentially useful for treatment of chronic AF in horses, the present study was undertaken to investigate the pharmacokinetics of orally and IV administered amiodarone in horses.
Limit of quantification
Limit of detection
Area under the curve to infinity
Volume of distribution
Terminal elimination t1/2
Maximum plasma concentration
Time to maximum plasma concentration
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Cordarone, Sanofi-Synthélabo, Belgium.
Sopachem, Brussels, Belgium.
Thermo Finnigan, San Jose, Calif.
Millipore, Brussels, Belgium.
M/W PHARM, version 3.60, Groningen, The Netherlands.
SPSS version 12.0, SPSS Inc, Headquarters SPSS, Chicago, Ill.
LCQ Advantage, Thermo Electron Corp, Brussels, Belgium.
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