Determination of oral dosage and pharmacokinetic analysis of flecainide in horses.
To determine oral dosage and to evaluate the pharmacokinetics in horses of orally administered flecainide, an antiarrhythmic drug, the correlations between its plasma concentration and PR, QRS and QT intervals in equine electrocardiograms (ECG) were investigated. Six healthy horses were administered a randomly ordered dose of 4 or 6 mg/kg of flecainide acetate. The ECG was monitored (heart rate (HR), PR, QRS, and QT intervals) and blood was taken at timed intervals to measure the plasma flecainide concentrations pre- and post-administration. The maximum plasma concentration reached 1014+/-285 (SD) ng/m/ in 45+/-13 min and 1301+/-400 ng/ m/l in 60+/-37 min for doses of 4 and 6 mg/kg flecainide, respectively. From the pharmacokinetic analysis, clearance rates were 14.6+/-6.4 and 11.7+/-5.2 ml/kg/min and terminal elimination half-lives were 228+/-53 and 304+/-87 min. The QRS and QT intervals increased significantly for both doses following administration, though HR and PR intervals did not change. Plasma flecainide concentrations were significantly correlated with QRS (r=0.935, P<0.001) and QT intervals (r=0.753, P<0.001). In conclusion, plasma concentrations of flecainide for treating equine atrial fibrillation were obtained by oral administration of 4 and 6 mg/kg, and the drug was rapidly eliminated from plasma in horses.
Ohmura
H
H
Equine Science Division, Hidaka Yearling Training Farm of Japan Racing Association (JRA), Hokkaido.
Hiraga
A
A
Aida
H
H
Takahashi
T
T
Nukada
T
T
D000284:Administration, Oral; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D004562:Electrocardiography / Q000662:veterinary; D005260:Female; D005424:Flecainide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006736:Horses / Q000378:metabolism*; D008297:Male; D011897:Random Allocation
D000889:Anti-Arrhythmia Agents; D005424:Flecainide