Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses.
Authors: Mercer M A, McKenzie H C, Davis J L, Wilson K E, Hodgson D R, Cecere T E, McIntosh B J
Journal: Equine veterinary journal
Summary
# Editorial Summary: Acetaminophen Pharmacokinetics and Safety in Horses Acetaminophen's clinical use in equine medicine has lacked evidence-based dosing guidance, with no prior pharmacokinetic data published at the 20 mg/kg dose routinely administered to horses or safety information regarding repeated dosing. Mercer and colleagues administered acetaminophen orally to eight healthy Thoroughbred geldings as a single 20 mg/kg dose, then twice daily for 14 consecutive days, measuring plasma drug concentrations via high-performance liquid chromatography and performing serum biochemistry, gastroscopy and liver biopsy to assess safety. Peak plasma concentration was approximately 16.6 µg/mL within 90 minutes of the single dose, with drug elimination half-life of 2.78 hours and undetectable levels within 24 hours; during the 14-day dosing period, no accumulation occurred despite twice-daily dosing, though elimination half-life extended slightly to 4 hours. Whilst sorbitol dehydrogenase activity decreased significantly and total bilirubin increased slightly following the final dose, gastroscopic examination revealed no mucosal damage and no other clinically concerning changes emerged from the safety monitoring. These findings provide reassurance that acetaminophen at 20 mg/kg can be administered safely for short-term analgesic use in adult horses, though the study's limitations—single dose level, small cohort, Thoroughbred geldings only, and absence of baseline liver biopsies—mean results should not be extrapolated to other breeds, ages or clinical populations without further investigation.
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Practical Takeaways
- •Acetaminophen 20 mg/kg can be safely dosed twice daily for up to 14 days in adult horses without clinically concerning drug accumulation
- •While acetaminophen shows gastrointestinal tolerance, monitor liver enzymes and bilirubin in horses receiving prolonged treatment due to observed biochemical changes
- •Drug is rapidly eliminated (below detection by 24 h single dose), supporting twice-daily dosing intervals for sustained analgesia
Key Findings
- •Single dose acetaminophen (20 mg/kg) achieved mean Cmax of 16.61 μg/mL at 1.35 h with T1/2 of 2.78 h
- •Multiple dosing twice daily for 14 days showed no significant drug accumulation with similar pharmacokinetic parameters (Cmax 15.85 μg/mL, T1/2 4 h)
- •Serum sorbitol dehydrogenase activity significantly decreased and total bilirubin concentrations significantly increased following repeated dosing
- •No statistically significant changes in gastroscopy scores, indicating repeated oral dosing was well-tolerated in the gastrointestinal tract