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Home / Equine Research Bank / J Vet Intern Med / Pharmacokinetics and efficacy of orally administered acetam...
Journal of veterinary internal medicine2023; 37(2); 718-727; doi: 10.1111/jvim.16663

Pharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia.

Abstract: Acetaminophen has been evaluated in horses for treatment of musculoskeletal pain but not as an antipyretic. Objective: To determine the pharmacokinetics and efficacy of acetaminophen compared to placebo and flunixin meglumine in adult horses with experimentally induced endotoxemia. Methods: Eight university owned research horses with experimentally induced endotoxemia. Methods: Randomized placebo controlled crossover study. Horses were treated with acetaminophen (30 mg/kg PO; APAP), flunixin meglumine (1.1 mg/kg, PO; FLU), and placebo (PO; PLAC) 2 hours after administration of LPS. Plasma APAP was analyzed via LC-MS/MS. Serial CBC, lactate, serum amyloid A, heart rate and rectal temperature were evaluated. Serum IL-1β, IL-6, IL-8, IL-10, and TNF-α were evaluated by an equine-specific multiplex assay. Results: Mean maximum plasma APAP concentration was 13.97 ± 2.74 μg/mL within 0.6 ± 0.3 hour after administration. At 4 and 6 hours after treatment, both APAP (P = <.001, P = .03, respectively) and FLU (P = .0045 and P < .001, respectively) had a significantly greater decrease in rectal temperature compared to placebo. FLU caused greater heart rate reduction than APAP at 4 and 6 hours (P = .004 and P = .04), and PLAC at 4 hours (P = .05) after treatment. Conclusions: The pharmacokinetics of acetaminophen in endotoxemic horses differ from those reported by previous studies in healthy horses. Acetaminophen is an option for antipyresis in clinical cases, particularly when administration of traditional NSAIDs is contraindicated.
© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.
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Publication Date: 2023-02-24 PubMed ID: 36840424PubMed Central: PMC10061170DOI: 10.1111/jvim.16663Google Scholar: Lookup
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  • Journal Article

Summary

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The study investigated the effects and absorption, distribution, metabolism, and excretion (pharmacokinetics) of acetaminophen in adult horses that were given a condition that introduces toxins into the blood (endotoxemia). The findings showed changed pharmacokinetics in these horses and revealed that acetaminophen could be a viable treatment option to reduce fever, especially when traditional non-steroidal anti-inflammatory drugs (NSAIDs) cannot be administered.

Study Design and Methodology

  • Eight adult horses owned by a university were treated with experimentally induced endotoxemia, where harmful toxins were introduced into their bloodstream.
  • A randomized placebo-controlled crossover study was conducted where horses were treated with acetaminophen, flunixin meglumine, and a placebo, two hours after being given a Lipopolysaccharides (LPS) injection.
  • The levels of acetaminophen in the horses’ plasma were measured via liquid chromatography-tandem mass spectrometry (LC-MS/MS).
  • Horse health indicators such as heart rate, rectal temperature, and blood lactate levels were monitored and analyzed.
  • They also analyzed serum levels of various interleukins and tumor necrosis factor-alpha (TNF-α), which are types of cytokines involved in immune response.

Results

  • The peak acetaminophen concentration in the horses’ plasma was found to occur roughly 0.6 hours after administration.
  • Four and six hours post-treatment, both acetaminophen and flunixin meglumine caused a significant drop in the horses’ rectal temperature compared to the placebo.
  • The heart rate reduction was greater with flunixin meglumine than with acetaminophen at four and six hours after treatment, as well as compared to the placebo at four hours post-treatment.
  • The findings suggest that acetaminophen pharmacokinetics in horses with experimentally induced endotoxemia are different from those in healthy horses.

Conclusions and Implications

  • The study concludes that acetaminophen could be used as a treatment to reduce fever in horses, especially in cases where traditional NSAIDs are not an option.
  • This research contributes to the understanding of acetaminophen pharmacokinetics in horses, especially those suffering from endotoxemia.

Cite This Article

APA
Mercer MA, Davis JL, McKenzie HC, Messenger KM, Schaefer E, Council-Troche RM, Werre SR. (2023). Pharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia. J Vet Intern Med, 37(2), 718-727. https://doi.org/10.1111/jvim.16663

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 37
Issue: 2
Pages: 718-727

Researcher Affiliations

Mercer, Melissa A
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Davis, Jennifer L
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
McKenzie, Harold C
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Messenger, Kristen M
  • Department of Molecular Biomedical Sciences, North Carolina State University College of Veterinary Medicine, Raleigh, North Carolina, USA.
Schaefer, Emily
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Council-Troche, R McAlister
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Werre, Stephen R
  • Department of Population Health Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.

MeSH Terms

  • Horses
  • Animals
  • Acetaminophen / therapeutic use
  • Acetaminophen / pharmacology
  • Endotoxemia / drug therapy
  • Endotoxemia / veterinary
  • Cross-Over Studies
  • Chromatography, Liquid / veterinary
  • Tandem Mass Spectrometry / veterinary
  • Horse Diseases

Grant Funding

  • Equine Research Competition / Virginia Maryland College of Veterinary Medicine

Conflict of Interest Statement

Authors declare no conflict of interest.

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