Pharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia.
Authors: Mercer Melissa A, Davis Jennifer L, McKenzie Harold C, Messenger Kristen M, Schaefer Emily, Council-Troche R McAlister, Werre Stephen R
Journal: Journal of veterinary internal medicine
Summary
# Editorial Summary Acetaminophen has potential as an antipyretic agent in horses with endotoxaemia, an important consideration given the limitations of NSAID use in certain clinical contexts. Researchers administered acetaminophen (30 mg/kg orally), flunixin meglumine (1.1 mg/kg orally), or placebo to eight horses with experimentally induced endotoxaemia, measuring plasma drug concentrations, inflammatory markers (cytokines and acute phase proteins), and clinical parameters including rectal temperature and heart rate over a 24-hour period. Both acetaminophen and flunixin reduced fever significantly compared to placebo at 4 and 6 hours post-treatment, though flunixin demonstrated superior heart rate reduction at these timepoints; acetaminophen reached peak plasma concentrations of approximately 14 μg/mL within 36 minutes. The pharmacokinetic profile of acetaminophen in endotoxaemic horses differed notably from previously published data in healthy animals, suggesting altered metabolism during systemic inflammation. These findings suggest acetaminophen warrants consideration as an antipyretic option when NSAIDs are contraindicated—whether due to renal compromise, concurrent medication interactions, or gastrointestinal concerns—though flunixin remains superior for concurrent heart rate modulation in endotoxic cases.
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Practical Takeaways
- •Acetaminophen (30 mg/kg PO) can effectively reduce fever in endotoxemic horses and may be considered when NSAIDs are contraindicated due to renal or gastrointestinal concerns
- •Flunixin meglumine remains superior for heart rate reduction during endotoxemia, so drug selection should consider whether temperature, pain, or cardiovascular stability is the primary treatment goal
- •Acetaminophen achieves therapeutic plasma levels quickly (within 36 minutes), making it a practical option for acute antipyretic therapy in equine practice
Key Findings
- •Mean maximum plasma acetaminophen concentration was 13.97 ± 2.74 μg/mL achieved within 0.6 ± 0.3 hours after 30 mg/kg oral administration
- •Both acetaminophen and flunixin meglumine significantly reduced rectal temperature compared to placebo at 4 and 6 hours post-treatment (P <0.001 to 0.03)
- •Flunixin meglumine caused greater heart rate reduction than acetaminophen at 4 and 6 hours post-treatment (P = 0.004 to 0.04)
- •Pharmacokinetics of acetaminophen in endotoxemic horses differ from previously reported values in healthy horses