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Home / Equine Research Bank / Equine Vet J / Pharmacokinetics and safety of repeated oral dosing of aceta...
Equine veterinary journal2019; 52(1); 120-125; doi: 10.1111/evj.13112

Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses.

Abstract: There are no published studies on the pharmacokinetics of acetaminophen at the dosage used clinically (20 mg/kg), nor has the safety of multiple doses in horses been investigated. Objective: Define the pharmacokinetic parameters of oral acetaminophen at 20 mg/kg in adult horses as a single dose, and twice daily for 14 days to assess the safety of multiple dosing. Methods: Pharmacokinetic study, multiple dose safety study. Methods: Eight healthy Thoroughbred geldings were given acetaminophen (20 mg/kg; 500 mg tablets) orally as a single dose followed by doses every 12 h for 14 days. Serial blood samples were collected for determination of plasma acetaminophen concentrations using high performance liquid chromatography with ultraviolet detection. Serum biochemical analysis, gastroscopy and liver biopsy were examined during the safety study. Results: Following a single dose, mean maximum concentration (C ) was 16.61 μg/mL at 1.35 h (T ), and drug concentration was below the lower limit of detection in most horses by 24 h. Elimination half-life (T ) was 2.78 h. No significant accumulation was noted following multiple doses. Average C of acetaminophen following multiple oral dosing was 15.85 μg/mL, with a T of 0.99 h and T of 4 h. Serum activities of sorbitol dehydrogenase were significantly decreased and total bilirubin concentrations were significantly increased following the last dose. No statistically significant changes were noted in gastroscopy scores. Conclusions: Only one dose level (20 mg/kg) was studied, sample size was small and only a single breed and sex was used, with no pretreatment liver biopsies. Conclusions: This study described the pharmacokinetics of acetaminophen following single and multiple 20 mg/kg oral doses in adult horses and demonstrated the safety of acetaminophen with multiple oral dosing over 14 days. The summary is available in Portuguese - see Supporting information.
© 2019 EVJ Ltd.
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Publication Date: 2019-04-16 PubMed ID: 30900298DOI: 10.1111/evj.13112Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article

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.

This research explores the effects and safety of repeated oral dosing of acetaminophen in adult horses. Initially, the study identified the pharmacokinetic parameters of a single 20 mg/kg acetaminophen dose and subsequently extended this to twice daily dosing over 14 days.

Research Methodology

  • Eight healthy Thoroughbred geldings, a single breed and sex subset, were administered acetaminophen at clinically relevant doses (20 mg/kg in 500 mg tablets) orally as a single dose, followed by two doses each day for two weeks.
  • Serial blood samples were taken to determine plasma acetaminophen concentrations, using high-performance liquid chromatography with ultraviolet detection.
  • To assess safety, the researchers conducted a serum biochemical analysis and also carried out a liver biopsy and gastroscopy.

Findings

  • A single dose showed a mean maximum concentration (C) of 16.61 μg/mL at 1.35 hours (T), and had mostly fallen below the detection limit by 24 hours. The recorded elimination half-life (T) was 2.78 hours.
  • No significant accumulation was observed following multiple doses. The average concentration (C) of acetaminophen after multiple oral doses was 15.85 μg/mL, with a recorded peak time (T) of 0.99 hours and elimination half-life (T) of 4 hours.
  • Serum activities of sorbitol dehydrogenase showed significant decrease following the last dose while total bilirubin concentrations significantly increased. No statistically significant changes were noted in gastroscopy scores, indicating minimal gastric effects.

Conclusions

  • The study outlines the pharmacokinetics of acetaminophen in horses after single and multiple oral doses, confirming its safety when dosed orally over two weeks.
  • Limitations include a focus on a single dose level, small sample size, and restriction to a single breed and sex. Despite these, the results showed promising pharmacokinetic values and safety profiles that warrant further exploration.

This study makes a significant contribution by describing the pharmacokinetics and safety of acetaminophen in horses.

Cite This Article

APA
Mercer MA, McKenzie HC, Davis JL, Wilson KE, Hodgson DR, Cecere TE, McIntosh BJ. (2019). Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses. Equine Vet J, 52(1), 120-125. https://doi.org/10.1111/evj.13112

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 52
Issue: 1
Pages: 120-125

Researcher Affiliations

Mercer, M A
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
McKenzie, H C
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Davis, J L
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Wilson, K E
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Hodgson, D R
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
Cecere, T E
  • Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, Virginia, USA.
McIntosh, B J
  • Department of Animal and Poultry Science, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, Virginia, USA.

MeSH Terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / adverse effects
  • Acetaminophen / blood
  • Acetaminophen / pharmacokinetics
  • Administration, Oral
  • Animals
  • Drug Administration Schedule
  • Half-Life
  • Horses / blood
  • Horses / metabolism
  • Male
  • Statistics as Topic

Grant Funding

  • Zoetis, Inc
  • 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. Gold JR, Grubb T, Court MH, Villarino NF. Pharmacokinetics of acetaminophen after a single Oral administration of 20 or 40 mg/kg to 7-9 Day-old foals.. Front Vet Sci 2023;10:1198940.
    doi: 10.3389/fvets.2023.1198940pubmed: 37483288google scholar: lookup
  3. 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
  4. Flood J, Stewart AJ. Non-Steroidal Anti-Inflammatory Drugs and Associated Toxicities in Horses.. Animals (Basel) 2022 Oct 26;12(21).
    doi: 10.3390/ani12212939pubmed: 36359062google scholar: lookup
  5. Ghajar SM, McKenzie H, Fike J, McIntosh B, Tracy BF. Evaluating digestibility and toxicity of native warm-season grasses for equines.. Transl Anim Sci 2021 Jan;5(1):txaa224.
    doi: 10.1093/tas/txaa224pubmed: 33501415google scholar: lookup
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