Pharmacokinetics, clinical efficacy and safety of acetaminophen (paracetamol) in adult horses with naturally occurring chronic lameness.
Abstract: Acetaminophen is used clinically in horses with musculoskeletal pain; however, no studies have been performed in horses with chronic lameness. Objective: To determine the pharmacokinetics, safety and efficacy of chronic dosing of acetaminophen in horses with naturally occurring chronic lameness. Methods: Longitudinal. Methods: Twelve adult horses with chronic lameness were treated with acetaminophen (30 mg/kg PO) every 12 h for 21 days. Plasma concentrations of acetaminophen were analysed on days 7 and 21 via LC-MS/MS and noncompartmental pharmacokinetic analysis. Lameness was evaluated by body-mounted inertial sensor (BMIS) and 10-point subjective lameness score on day 21 and compared to untreated baseline evaluation on day 35. Clinicopathological analysis (n = 12), hepatic biopsy (n = 6) and gastroscopy (n = 6) were evaluated on days -1 and 22. Results: Maximum plasma acetaminophen concentration (Cmax ) was 20.83 ± 10.25 μg/mL at time (Tmax ) 0.40 ± 0.22 h on day 7. The Cmax on day 21 was 17.33 ± 6.91 μg/mL with a Tmax of 0.67 ± 0.26 h. Subjective lameness scores significantly improved at 2 and 4 h post-treatment; Significant percent improvement was detected in PDmax for horses with hindlimb lameness at 1, 2 and 8 h post-treatment. There were no significant differences in gastroscopy or hepatic biopsy scores between days -1 and 22. Conclusions: Small sample size, multi-limb lameness of varying severity and aetiology, lack of intermediary lameness evaluation. Conclusions: In horses with naturally occurring chronic lameness, acetaminophen at 30 mg/kg produced a transient improvement in subjective lameness and BMIS evaluation. Acetaminophen may not be effective as a monotherapy. Acetaminophen was safe following 21 days of 30 mg/kg PO every 12 h, with no evidence of clinically significant changes in clinicopathological analysis, hepatic biopsy or gastric ulceration scores.
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Publication Date: 2023-06-07 PubMed ID: 37287331DOI: 10.1111/evj.13959Google Scholar: Lookup
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- Journal Article
Summary
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This study examined the use of acetaminophen in treating long-term lameness in horses. It highlighted that while it provided some temporary improvements, it may not be a lasting solution, but it is safe for the animals with no significant health concerns detected after 21 days of use.
Methods
- The study adopted a longitudinal approach, and subjects consisted of twelve adult horses with a history of chronic lameness.
- These horses were administered acetaminophen orally every twelve hours for twenty-one days at a dose of 30mg/kg.
- Blood samples were then taken from the horses on days seven and twenty-one and analysed for plasma concentrations of acetaminophen using liquid chromatography-tandem mass spectrometry and noncompartmental pharmacokinetic analysis.
- A body-mounted inertial sensor (BMIS) assessed lameness in the horses. Additionally, a ten-point subjective lameness score was also used on the twenty-first day and compared to the untreated baseline evaluation conducted on the thirty-fifth day.
- For complete safety and health evaluations, clinicopathological analysis, hepatic biopsies and gastroscopies were carried out on days negative one and twenty-two.
Results
- The blood analysis from day seven reflected a maximum plasma acetaminophen concentration of 20.83 ± 10.25 μg/mL after approximately 0.40 ± 0.22 hours. On day twenty-one, the concentration dropped to 17.33 ± 6.91 μg/mL, with a time of approximately 0.67 ± 0.26 hours.
- The researchers noted a significant improvement in lameness scores at two and four hours post-treatment. Substantial improvements were also detected in horses with hindlimb lameness at one, two, and eight hours post-therapy.
- There were no significant differences found from the gastroscopy or hepatic biopsy scores between the first and the twenty-second day, indicating the treatment had no adverse effects on the horses over this period.
Conclusions
- The study concluded that while acetaminophen yielded certain transient improvements in lameness in horses, it might not be effective as a standalone therapy.
- It was also highlighted that despite small sample size, multi-limb lameness severity and etiology variability, acetaminophen appeared safe following administration at doses of 30 mg/kg every twelve hours for twenty-one days.
- No clinically significant changes were observed in any of the health evaluations – clinicopathological analysis, hepatic biopsy or gastric ulceration assessments.
Cite This Article
APA
Mercer MA, Davis JL, McKenzie HC, Byron CR, Kelleher ME, Trager L, Cecere TE, Wilson KE, Council-Troche RM, Werre SR.
(2023).
Pharmacokinetics, clinical efficacy and safety of acetaminophen (paracetamol) in adult horses with naturally occurring chronic lameness.
Equine Vet J, 56(1), 202-214.
https://doi.org/10.1111/evj.13959 Publication
Researcher Affiliations
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
- Department of Large Animal Clinical Sciences, Marion duPont Scott Equine Medical Center, Leesburg, Virginia, USA.
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
- Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
- Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia, USA.
- Department of Population Health Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
MeSH Terms
- Horses
- Animals
- Acetaminophen / adverse effects
- Lameness, Animal / drug therapy
- Chromatography, Liquid / veterinary
- Horse Diseases / drug therapy
- Horse Diseases / pathology
- Tandem Mass Spectrometry / veterinary
- Treatment Outcome
Grant Funding
- VIrginia-Maryland College of Veterinary Medicine Veterinary Memorial Fund
- Zoetis, Inc
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