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Equine veterinary journal2022; 55(3); 524-533; doi: 10.1111/evj.13601

Pharmacokinetics and clinical efficacy of acetaminophen (paracetamol) in adult horses with mechanically induced lameness.

Abstract: Acetaminophen has been used clinically in horses alone or combined with traditional non-steroidal anti-inflammatory drugs for treatment of musculoskeletal pain in horses. Objective: To determine the pharmacokinetics and efficacy of acetaminophen at two doses in horses with mechanically induced lameness compared with phenylbutazone or placebo control. Methods: In vivo experiment. Methods: Nine healthy mares with mechanical lameness induced via a reversible sole pressure horseshoe model were treated with acetaminophen (20 mg/kg PO; A20), acetaminophen (30 mg/kg PO; A30), phenylbutazone (2.2 mg/kg, PO; PB) and oral placebo (C) in a randomised four-way Latin square model. Plasma concentrations for A20 and A30 were analysed via LC-MS/MS and noncompartmental pharmacokinetic analysis. Heart rate and heart rate variability were measured using a portable telemetry. Lameness was scored by three blinded boarded equine surgeons using the AAEP and 10-point scales. Results: Mean maximum plasma concentration (C ) for A20 was 20.01 μg/ml within 0.66 h (T ) after administration; The mean C for A30 was 30.02 μg/ml with a T of 0.43 h. Post-treatment heart rate for A30 was significantly lower than A20 at 1 and 7 h; lower than PB at 2, 3, 4.5 and 7 h; lower than C at 2, 3.5, 4.5, 6, 7 and 8 h. 10-point Lameness scores were significantly improved for A30 than C at 2 and 4 h post-treatment; PB was significantly improved than C at 8 h post treatment. There were no significant differences in lameness between A20, A30 and PB. Conclusions: Small sample size, lack of objective lameness measurement. Conclusions: Acetaminophen at 30 mg/kg produced a more rapid improvement in lameness scores and heart rate compared with other treatments in this model. Further evaluation of the pharmacokinetics and safety of repeated oral dosing of acetaminophen at 30 mg/kg is needed to determine clinical utility. Unassigned: Acetaminofeno tem sido usado rotineiramente em cavalos com dor musculoesquelética, tanto como terapia solo quanto em associação com outros anti-inflamatórios não esteroides tradicionais. Objective: Determinar a farmacocinética e eficácia de duas doses de acetaminofeno em cavalos com claudicação mecanicamente induzida, e comparar com fenilbutazona e placebo. Unassigned: Estudo randomizado, cego e controlado utilizando quadrado latino. Methods: Nove éguas adultas com claudicação induzida mecanicamente pelo método de aplicação de pressão na sola através de ferradura foram tratadas com acetaminofeno (20 mg/kg VO; A20), acetaminofeno (30 mg/kg VO; A30), fenilbutazona (2.2 mg/kg, VO; PB) e placebo oral (C) em um estudo quadrado latino de forma randômica. Concentração plasmática dos grupos A20 e A30 foram analisadas pelo método LC-MS/MS e análise farmacocinética não compartimentar. Frequência cardíaca e variação da frequência cardíaca foram mensuradas usando telemetria portátil. O grau de claudicação foi avaliado usando a escala de 10 pontos da AAEP por três cirurgiões especialistas (board-certified) que estavam cegos ao tratamento. Results: A média máxima da concentração plasmática (C ) do grupo A20 foi 20.01 μg/ml dentro de 0.66 h (T ) da administração. A média C do grupo A30 foi 30.02 μg/ml dentro da T de 0.43 h. A frequência cardíaca do grupo A30 foi significativamente mais baixa do que a do grupo A20 nos momentos 1 e 7 h; mais baixa do que o grupo PB nos momentos 2, 3, 4.5 e 7 h; e mais baixa do que as do grupo C nos momentos 2, 3.5, 4.5, 6, 7 e 8 h. O grau de claudicação diminuiu significativamente no grupo A30 quando comparado com o grupo C nos momentos 2 e 4 h pós tratamento, e no grupo PB quando comparado com o grupo C no momento 8 h pós tratamento. Não houve diferença significativa em grau de claudicação quando os grupos A20, A30 e PB foram comparados. PRINCIPAIS LIMITAÇÕES: Número pequeno de animais, ausência de mensuração de claudicação objetiva. CONCLUSÕES: A dose de 30 mg/kg de acetaminofeno proporcionou uma superior melhora na escala de claudicação e frequência cardíaca quando comparada com os outros tratamentos avaliados neste estudo. Mais informações sobre a farmacocinética e efeitos da repetida dosagem de 30 mg/kg de acetaminofeno precisam ser avaliadas para determinar a sua aplicabilidade clínica.
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Publication Date: 2022-06-24 PubMed ID: 35633196DOI: 10.1111/evj.13601Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research explores the effectiveness and pharmacokinetics (how the body absorbs, distributes, metabolizes, and excretes a drug) of acetaminophen (paracetamol) on treating mechanically induced lameness in horses. Higher doses of acetaminophen resulted in rapid improvement in lameness scores and heart rate compared with other treatments.

Methods

  • The study used nine healthy adult mares (female horses) with mechanically induced lameness. The lameness was induced by applying pressure on the sole of the horse’s foot using a special horseshoe.
  • These horses were then given acetaminophen (at 20 mg/kg and 30 mg/kg), phenylbutazone (a traditional non-steroidal anti-inflammatory drug), or a placebo in a randomized sequence.
  • Plasma concentration of acetaminophen at the two doses was measured using liquid chromatography-mass spectrometry (LC-MS/MS), a widely accepted method for drug detection. The study also made use of noncompartmental pharmacokinetic analysis which involves analyzing the concentration of the drug in the bloodstream over time.
  • Heart rate and heart rate variability were also measured using portable telemetry, and lameness was scored using standard scales by three blinded veterinary surgeons.

Results

  • The plasma concentration peak time for the 30 mg/kg dose of acetaminophen (A30) was shorter (0.43 hr) compared to the 20 mg/kg dose (A20) which was 0.66 hr.
  • The heart rate post-treatment with A30 was significantly lower than A20 at 1 and 7 hours, lower than phenylbutazone (PB) at 2, 3, 4.5 and 7 hours, and lower than placebo (C) at multiple time points. This suggests that A30 had a relaxing effect on horses.
  • Lameness scores were significantly improved for A30 compared to the placebo at 2 and 4 hours post-treatment. At 8 hours post-treatment, lameness scores were significantly better for phenylbutazone than the placebo.
  • There were no significant differences in lameness between A20, A30, and PB, indicating a beneficial effect of the drug under study.

Limitations & Conclusions

  • The study was small and lacked objective lameness measurement. More research with larger sample sizes may be needed to verify these findings.
  • In conclusion, it was found that 30 mg/kg dose of acetaminophen helped in rapid improvement in lameness and decrease in heart rate, making it potentially beneficial for managing musculoskeletal pain in horses.
  • Future studies need to further evaluate pharmacokinetics and safety of repeatedly administering the 30 mg/kg dose of acetaminophen to confirm these findings and establish its clinical applicability.

Cite This Article

APA
Mercer MA, McKenzie HC, Byron CR, Pleasant RS, Bogers SH, Council-Troche RM, Werre SR, Burns T, Davis JL. (2022). Pharmacokinetics and clinical efficacy of acetaminophen (paracetamol) in adult horses with mechanically induced lameness. Equine Vet J, 55(3), 524-533. https://doi.org/10.1111/evj.13601

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 55
Issue: 3
Pages: 524-533

Researcher Affiliations

Mercer, Melissa A
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
McKenzie, Harold C
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
Byron, Christopher R
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
Pleasant, Robert S
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
Bogers, Sophie H
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
Council-Troche, Roberto M
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
Werre, Stephen R
  • Department of Population Health Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
Burns, Travis
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
Davis, Jennifer L
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.

MeSH Terms

  • Animals
  • Female
  • Acetaminophen / therapeutic use
  • Chromatography, Liquid / veterinary
  • Horse Diseases / drug therapy
  • Horses
  • Lameness, Animal / drug therapy
  • Phenylbutazone / pharmacokinetics
  • Tandem Mass Spectrometry / veterinary
  • Treatment Outcome

Grant Funding

  • The Virginia Horse Industry Board

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Citations

This article has been cited 5 times.
  1. Patton ME, Andrews FM, Bogers SH, Wong D, McKenzie HC 3rd, Werre SR, Byron CR. Effects of Bit Chewing on Gastric Emptying, Small Intestinal Transit, and Orocecal Transit Times in Clinically Normal Horses. Animals (Basel) 2023 Aug 4;13(15).
    doi: 10.3390/ani13152518pubmed: 37570326google scholar: lookup
  2. Mercer MA, Davis JL, McKenzie HC. The Clinical Pharmacology and Therapeutic Evaluation of Non-Steroidal Anti-Inflammatory Drugs in Adult Horses. Animals (Basel) 2023 May 10;13(10).
    doi: 10.3390/ani13101597pubmed: 37238029google scholar: lookup
  3. Mercer MA, Davis JL, McKenzie HC, Messenger KM, Schaefer E, Council-Troche RM, Werre SR. Pharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia. J Vet Intern Med 2023 Mar;37(2):718-727.
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