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Equine veterinary journal2026; doi: 10.1002/evj.70315

Analgesic use, safety and pharmacokinetics of acetaminophen in equids: A structured scoping review.

Abstract: Despite its frequent use in equine clinical practice, scientific data on the use of acetaminophen in horses remain limited. Objective: To map and critically appraise the available evidence on the analgesic use, safety and pharmacokinetics of acetaminophen in horses. Methods: Structured scoping review. Methods: A comprehensive search was performed in accordance with the PRISMA Extension for Scoping Reviews using the terms '(paracetamol OR acetaminophen) AND (pain OR safety OR toxicosis OR pharmacokinetics) AND (horse OR pony OR donkey OR mule)' across Web of Science, Scopus, and PubMed from database inception to 27 July 2025. Experimental and clinical studies, reviews and case reports evaluating acetaminophen in equids were eligible. Publications without acetaminophen information about analgesia, safety or pharmacokinetics in horses were excluded. Each article was screened and charted according to study design, level of evidence (LoE) (methodological robustness) and thematic domain by two evaluators. Results: Of the initial 45 articles, 27 met eligibility criteria. Ten studies were classified as LoE 1, six as LoE 2, seven as LoE 3, and four as LoE 5. Based on study design and thematic domain, the included publications comprised four categorised as 'case reports', seven as 'narrative reviews', one as 'prospective comparative studies', 11 as 'pharmacokinetics', and four as 'pharmacokinetics and concentration-effect relationship'. Conclusions: Limited number of clinical studies and heterogeneity of available evidence. Conclusions: This review highlights the growing but still limited evidence on acetaminophen use in horses. While pharmacokinetic data are robust, clinical trials remain scarce and underpowered. Acetaminophen appears promising as part of multimodal analgesia, yet its efficacy as a sole agent and long-term safety require further investigation before widespread clinical adoption.
© 2026 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2026-08-23 PubMed ID: 42634193DOI: 10.1002/evj.70315Google Scholar: Lookup
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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.

Overview

  • This research article systematically reviews existing scientific evidence on the use, safety, and pharmacokinetics of acetaminophen (paracetamol) in horses and other equids.
  • It highlights the current knowledge gaps and evaluates the quality of available studies to guide future research and clinical application.

Background and Objectives

  • Acetaminophen is frequently used as an analgesic in equine veterinary practice, but the scientific data supporting its use in horses remain limited.
  • The objective was to comprehensively map and critically assess evidence concerning three major themes in equids:
    • Analgesic use (effectiveness in pain relief)
    • Safety (toxicity and adverse effects)
    • Pharmacokinetics (how the drug is absorbed, distributed, metabolized, and eliminated)

Methods

  • The authors conducted a structured scoping review following PRISMA-ScR guidelines to ensure transparency and rigor.
  • They searched major databases (Web of Science, Scopus, PubMed) up to July 27, 2025, using specific search terms linking acetaminophen with equids and key concepts like pain, safety, toxicosis, and pharmacokinetics.
  • Inclusion criteria:
    • Studies involving horses, ponies, donkeys or mules
    • Research that assessed acetaminophen’s analgesic use, safety profile, or pharmacokinetics
    • Various study types included: experimental studies, clinical trials, reviews, and case reports
  • Excluded were studies lacking relevant data on acetaminophen use in equids for these specific domains.
  • Two reviewers independently screened and extracted data, classifying studies by:
    • Study design (e.g., case report, clinical trial, pharmacokinetics)
    • Level of evidence (LoE) indicating methodological quality, ranging from 1 (highest) to 5 (lowest)
    • Thematic content related to analgesia, safety, or pharmacokinetics

Results

  • Out of 45 initially identified articles, 27 met the eligibility criteria for inclusion.
  • Levels of evidence among included studies:
    • LoE 1 (highest quality): 10 studies
    • LoE 2: 6 studies
    • LoE 3: 7 studies
    • LoE 5 (lowest quality): 4 studies
  • Classification by study design and focus:
    • Case reports: 4
    • Narrative reviews: 7
    • Prospective comparative studies: 1
    • Pharmacokinetics-focused studies: 11
    • Pharmacokinetics plus concentration-effect (efficacy) relationship: 4

Key Findings

  • Pharmacokinetics:
    • The pharmacokinetic profile of acetaminophen in horses is relatively well characterized by multiple studies, providing robust data on how the drug behaves in equids.
    • This includes absorption rates, bioavailability, metabolism, half-life, and excretion.
  • Analgesic Use:
    • Clinical trials directly testing the analgesic efficacy of acetaminophen in horses are scarce (only one notable prospective comparative study).
    • Evidence suggests acetaminophen may be useful as part of multimodal analgesia (combined with other pain-relieving modalities), but its effectiveness as a sole analgesic agent remains unclear.
  • Safety:
    • Few studies and reports address the safety and potential toxicity of acetaminophen in horses.
    • Long-term safety data are lacking, which is important given the drug’s known adverse effects in other species at high doses or extended use.

Conclusions and Implications

  • The review reveals a growing body of research on acetaminophen in equids but still highlights significant gaps, particularly in clinical efficacy and safety data.
  • Pharmacokinetic studies provide a solid foundation for dosing considerations but do not substitute for clinical trial evidence on pain control effectiveness.
  • Before acetaminophen can be widely recommended as a single analgesic agent in equine veterinary practice, further well-designed clinical trials are needed to:
    • Confirm its analgesic potency when used alone
    • Assess safety during prolonged use
    • Compare its efficacy to other licensed analgesics
  • For now, acetaminophen may be considered as part of a multimodal pain management strategy in horses, but veterinarians should remain cautious given limited evidence.

Cite This Article

APA
Medina-Bautista F, Serrano-Rodríguez JM, Granados MDM. (2026). Analgesic use, safety and pharmacokinetics of acetaminophen in equids: A structured scoping review. Equine Vet J. https://doi.org/10.1002/evj.70315

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Medina-Bautista, Francisco
  • Section of Anaesthesiology, Department of Animal Medicine and Surgery, Veterinary Teaching Hospital, Universidad de Córdoba, Córdoba, Spain.
Serrano-Rodríguez, Juan Manuel
  • Pharmacology Area, Department of Nursing, Pharmacology and Physiotherapy, Veterinary Faculty, Universidad de Córdoba, Córdoba, Spain.
Granados, María Del Mar
  • Section of Anaesthesiology, Department of Animal Medicine and Surgery, Veterinary Teaching Hospital, Universidad de Córdoba, Córdoba, Spain.

References

This article includes 61 references
  1. Molony V, Kent JE. Assessment of acute pain in farm animals using behavioral and physiological measurements. J Anim Sci 1997;75:266–272.
    doi: 10.2527/1997.751266xgoogle scholar: lookup
  2. Torcivia C, McDonnell S. In‐person caretaker visits disrupt ongoing discomfort behavior in hospitalized equine orthopedic surgical patients. Animals (Basel) 2020;10(2):210.
    doi: 10.3390/ani10020210google scholar: lookup
  3. Taylor PM, Pascoe PJ, Mama KR. Diagnosing and treating pain in the horse: where are we today?. Vet Clin North Am Equine Pract 2002;18(1):1–19.
    doi: 10.1016/s0749-0739(02)00009-3google scholar: lookup
  4. Sanchez LC, Robertson SA. Pain control in horses: what do we really know?. Equine Vet J 2014;46(4):517–523.
    doi: 10.1111/evj.12265google scholar: lookup
  5. Davis JL. Nonsteroidal anti‐inflammatory drug associated right dorsal colitis in the horse. Equine Vet Educ 2015;29(2):104–113.
    doi: 10.1111/eve.12454google scholar: lookup
  6. Flood J, Stewart AJ. Non‐steroidal anti‐inflammatory drugs and associated toxicities in horses. Animals 2022;12(21):2939.
    doi: 10.3390/ani12212939google scholar: lookup
  7. Clutton RE. Opioid analgesia in horses. Vet Clin North Am Equine Pract 2010;26(3):493–514.
    doi: 10.1016/j.cveq.2010.07.002google scholar: lookup
  8. Haralambus R, Juri M, Mokry A, Jenner F. The impact of opioid administration on the incidence of postanaesthetic colic in horses. Front Pain Res 2024;5:1347548.
    doi: 10.3389/fpain.2024.1347548google scholar: lookup
  9. Bowen IM, Redpath A, Dugdale A, Burford JH, Lloyd D, Watson T. BEVA primary care clinical guidelines: Analgesia. Equine Vet J 2020;52(1):13–27.
    doi: 10.1111/evj.13198google scholar: lookup
  10. Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF. The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings. Inflammopharmacology 2013;21(3):201–232.
    doi: 10.1007/s10787-013-0172-xgoogle scholar: lookup
  11. Graham GG, Scott KF. Mechanism of action of paracetamol. Am J Ther 2005;12(1):46–55.
    doi: 10.1097/00045391-200501000-00008google scholar: lookup
  12. Chandrasekharan NV, Dai H, Roos KL, Evanson NK, Tomsik J, Elton TS. COX‐3, a cyclooxygenase‐1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc Natl Acad Sci USA 2002;99(21):13926–13931.
    doi: 10.1073/pnas.162468699google scholar: lookup
  13. Hernández‐Avalos I, Valverde A, Ibancovichi‐Camarillo JA, Sánchez‐Aparicio P, Recillas‐Morales S, Osorio‐Avalos J. Clinical evaluation of postoperative analgesia, cardiorespiratory parameters and changes in liver and renal function tests of paracetamol compared to meloxicam and carprofen in dogs undergoing ovariohysterectomy. PLoS One 2020;15(2):e0223697.
    doi: 10.1371/journal.pone.0223697google scholar: lookup
  14. Högestätt ED, Jönsson BAG, Ermund A, Andersson DA, Björk H, Alexander JP. Conversion of acetaminophen to the bioactive N‐acylphenolamine AM404 via fatty acid amide hydrolase‐dependent arachidonic acid conjugation in the nervous system. J Biol Chem 2005;280(36):31405–31412.
    doi: 10.1074/jbc.m501489200google scholar: lookup
  15. Alloui A, Chassaing C, Schmidt J, Ardid D, Dubray C, Cloarec A. Paracetamol exerts a spinal, tropisetron‐reversible, antinociceptive effect in an inflammatory pain model in rats. Eur J Pharmacol 2002;442(1–3):1–7.
    doi: 10.1016/j.ejphar.2006.03.048google scholar: lookup
  16. Smith HS. Potential analgesic mechanisms of acetaminophen.. Pain Physician 2009;12(1):269–280.
  17. de Kock SS, Mandy K, Martinovic ST, Jogi P, Guthrie AJ. A study of paracetamol, orthocetamol and metacetamol in horseracing in Southern Africa.. In: Houghton E, Ipek Keskin F, Wade JF, Yazicioglu N, editors. Proceedings of the 17th International Conference of Racing Analysts and Veterinarians, Antalya, Turkey, 2008. Newmarket: R&W Publications (Newmarket) Ltd.; 2009. p. 363–369.
  18. Mercer MA, McKenzie HC, Davis JL, Wilson KE, Hodgson DR, Cecere TE. Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses.. Equine Vet J 2020;52(1):120–125.
    doi: 10.1111/evj.13112google scholar: lookup
  19. Mercer MA, Davis JL, McKenzie HC. Pharmacokinetics and efficacy of orally administered acetaminophen (paracetamol) in adult horses with experimentally induced endotoxemia.. J Vet Intern Med 2023b;37(2):718–727.
    doi: 10.1111/jvim.16663google scholar: lookup
  20. Mercer MA, McKenzie HC, Byron CR. Pharmacokinetics and clinical efficacy of acetaminophen (paracetamol) in adult horses with mechanically induced lameness.. Equine Vet J 2023c;55(3):524–533.
    doi: 10.1111/evj.13601google scholar: lookup
  21. Tueshaus T, McKemie DS, Kanarr K, Kass PH, Knych HK. Pharmacokinetics and effects of codeine in combination with acetaminophen on thermal nociception in horses.. J Vet Pharmacol Ther 2023;46(5):311–325.
    doi: 10.1111/jvp.13126google scholar: lookup
  22. Mercer MA, Davis JL, McKenzie HC, Byron CR, Kelleher ME, Trager L. Pharmacokinetics, clinical efficacy and safety of acetaminophen (paracetamol) in adult horses with naturally occurring chronic lameness.. Equine Vet J 2024;56(1):202–214.
    doi: 10.1111/evj.13959google scholar: lookup
  23. Tricco AC, Lillie E, Zarin W, O'Brien KK, Colquhoun H, Levac D. PRISMA extension for scoping reviews (PRISMA‐ScR): checklist and explanation.. Ann Intern Med 2018;169(7):467–473.
    doi: 10.7326/m18-0850google scholar: lookup
  24. Hydrocephalus Association. Research 101: Levels of evidence in hydrocephalus clinical research studies.. Hydroassoc.org. 2024 [cited 2024 Apr 27]. Available from: https://www.hydroassoc.org/research-101-levels-of-evidence-in-hydrocephalus-clinical-research-studies/.
  25. Bruniges N, Milner P, Bardell D. The use of multimodal analgesia in the management of suspected compartment syndrome in a horse.. Equine Vet Educ 2017;31(7):354–362.
    doi: 10.1111/eve.12797google scholar: lookup
  26. Tallon R, McMillan M, Ho N, Dunkel B. Presumed generalised seizure following caudal epidural administration of morphine and detomidine in a pony.. Equine Vet Educ 2020;33(10):372–375.
    doi: 10.1111/eve.13342google scholar: lookup
  27. West E, Bardell D, Morgan R, Senior M. Use of acetaminophen (paracetamol) as a short‐term adjunctive analgesic in a laminitic pony.. Vet Anaesth Analg 2011;38(5):521–522.
    doi: 10.1111/j.1467-2995.2011.00639.xgoogle scholar: lookup
  28. Pfeifle RL, Beasley EM, Crabtree NE, Fraser C, Elbert JA, Ducker E. Osteosarcoma in the femur of a horse.. Equine Vet Educ 2021;33(11):411–415.
    doi: 10.1111/eve.13445google scholar: lookup
  29. Bardell D. Managing orthopaedic pain in horses.. In Pract 2017;39(9):420–427.
    doi: 10.1136/inp.j4169google scholar: lookup
  30. Foreman JH. A review of objective assessments of orthopaedic analgesic efficacy of non‐steroidal anti‐inflammatory drugs in horses.. Comp Exerc Physiol 2017;10(3):195–204.
    doi: 10.3920/cep160035google scholar: lookup
  31. van Loon JPAM. Multimodal analgesia, a fashionable term or evidence‐based medicine?. Equine Vet Educ 2019;31(7):363–364.
    doi: 10.1111/eve.12822google scholar: lookup
  32. De Laat MA, Sillence MN. A review of recent developments in the pharmacological prevention and treatment of endocrinopathic laminitis. Anim Prod Sci 2020;60:2081–2092.
    doi: 10.1071/an19491google scholar: lookup
  33. Rhodes DM, Madrigal R. Management of colic in the field. Vet Clin North Am Equine Pract 2021;37(2):421–439.
    doi: 10.1016/j.cveq.2021.04.010google scholar: lookup
  34. Mackenzie C. Clinical insights: equine analgesia. Equine Vet J 2021;53(3):407–409.
    doi: 10.1111/evj.13421google scholar: lookup
  35. Mercer MA, Davis JL, McKenzie HC. The clinical pharmacology and therapeutic evaluation of non‐steroidal anti‐inflammatory drugs in adult horses. Animals 2023a;13(10):1597.
    doi: 10.3390/ani13101597google scholar: lookup
  36. Tavanaeimanesh H, Azarnoosh A, Ashar FS, Dehghan MM, Mohebbi Z, Akbarinejad V. Comparison of analgesic effects of a constant rate infusion of both tramadol and acetaminophen versus those of infusions of each individual drug in horses. J Equine Vet Sci 2018;64:101–106.
    doi: 10.1016/j.jevs.2018.02.015google scholar: lookup
  37. Neirinckx E, Vervaet C, De Boever S, Remon JP, Gommeren K, Daminet S. Species comparison of oral bioavailability, first‐pass metabolism and pharmacokinetics of acetaminophen. Res Vet Sci 2010;89(1):113–119.
    doi: 10.1016/j.rvsc.2010.02.002google scholar: lookup
  38. Engelking LR, Blyden GT, Lofstedt J, Greenblatt DJ. Pharmacokinetics of antipyrine, acetaminophen and lidocaine in fed and fasted horses. J Vet Pharmacol Ther 1987;10(1):73–82.
    doi: 10.1111/j.1365-2885.1987.tb00079.xgoogle scholar: lookup
  39. Pesko B, Habershon‐Butcher J, Muir T, Gray B, Taylor P, Fenwick S. Pharmacokinetics of paracetamol in the Thoroughbred horse following an oral multi‐dose administration. J Vet Pharmacol Ther 2022;45(1):54–62.
    doi: 10.1111/jvp.13024google scholar: lookup
  40. Peraza J, Hector RC, Lee S, Terhaar HM, Knych HK, Wotman KL. Ocular penetration of oral acetaminophen in horses. Equine Vet J 2023;55(5):899–904.
    doi: 10.1111/evj.13902google scholar: lookup
  41. Gold JR, Grubb T, Court M, Villarino NF. Pharmacokinetics of single dose administration of three increasing doses of acetaminophen per os in 1–3‐month‐old foals. Equine Vet J 2023a;55(5):891–898.
    doi: 10.1111/evj.13903google scholar: lookup
  42. 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 2023b;6(10):1198940.
    doi: 10.3389/fvets.2023.1198940google scholar: lookup
  43. Faivre C, Wong DM, Villarino NF, Court M, Gold JR. Pharmacokinetics of multiple oral doses of acetaminophen in equine neonates. Am J Vet Res 2023;84(9):ajver.23.04.0079.
    doi: 10.2460/ajvr.23.04.0079google scholar: lookup
  44. Ishii H, Obara T, Kijima‐Suda I. Investigation of plasma concentrations of paracetamol, metacetamol, and orthocetamol in Japanese racehorses using liquid chromatography–electrospray ionisation–tandem mass spectrometry. Drug Test Anal 2020;12(7):929–937.
    doi: 10.1002/dta.2792google scholar: lookup
  45. Ishii H, Obara T, Kusano K, Kijima‐Suda I. Quantitative analysis of paracetamol, metacetamol, and orthocetamol in equine urine from racehorses in Japan using liquid chromatography–electrospray ionisation–tandem mass spectrometry. Drug Test Anal 2020;12(8):1196–1202.
    doi: 10.1002/dta.2860google scholar: lookup
  46. Granados MM, Medina‐Bautista F, Navarrete‐Calvo R, Argüelles D, Domínguez‐Pérez JM, Priego‐Capote F. Population pharmacokinetics and clinical evaluation of intravenous acetaminophen and its metabolites in Andalusian horses. Vet J 2025;312:106357.
    doi: 10.1016/j.tvjl.2025.106357google scholar: lookup
  47. Pickering G, Loriot MA, Libert F, Eschalier A, Beaune P, Dubray C. Analgesic effect of acetaminophen in humans: first evidence of a central serotonergic mechanism. Clin Pharmacol Ther 2006;79(4):371–378.
    doi: 10.1016/j.clpt.2005.12.307google scholar: lookup
  48. Burns PB, Rohrich RJ, Chung KC. The levels of evidence and their role in evidence‐based medicine. Plast Reconstr Surg 2011;128(1):305–310.
    doi: 10.1097/prs.0b013e318219c171google scholar: lookup
  49. Green BN, Johnson CD, Adams A. Writing narrative literature reviews for peer‐reviewed journals: secrets of the trade. J Chiropr Med 2006;5(3):101–117.
    doi: 10.1016/s0899-3467(07)60142-6google scholar: lookup
  50. Wong T, Stang AS, Ganshorn H, Hartling L, Maconochie IK, Thomsen AM. Combined and alternating paracetamol and ibuprofen therapy for febrile children. Cochrane Database Syst Rev 2013;2013(10):CD009572.
    doi: 10.1002/14651858.cd009572.pub2google scholar: lookup
  51. Bello S, Krogsbøll LT, Gruber J, Zhao ZJ, Fischer D, Hróbjartsson A. Lack of blinding of outcome assessors in animal model experiments implies risk of observer bias. J Clin Epidemiol 2014;67(9):973–983.
    doi: 10.1016/j.jclinepi.2014.04.008google scholar: lookup
  52. Pound P, Bracken MB. Is animal research sufficiently evidence based to be a cornerstone of biomedical research?. BMJ 2014;348:g3387.
    doi: 10.1136/bmj.g3387google scholar: lookup
  53. Anderson BJ, Holford NHG, Woollard GA, Chan PLS. Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children. Br J Clin Pharmacol 1998;46(3):237–243.
    doi: 10.1046/j.1365-2125.1998.00780.xgoogle scholar: lookup
  54. Toutain PL, Lees P. Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine. J Vet Pharmacol Ther 2004;27(6):467–477.
    doi: 10.1111/j.1365-2885.2004.00613.xgoogle scholar: lookup
  55. Tarling MM, Toner CC, Withington PS, Baxter MK, Whelpton R, Goldhill DR. A model of gastric emptying using paracetamol absorption in intensive care patients. Intensive Care Med 1997;23(3):256–260.
    doi: 10.1007/s001340050325google scholar: lookup
  56. Mozaffari AA, Jarakanibayat S, Vosough D, Tajic J. The effect of the endotoxemia on the abomasal emptying rate in suckling lambs as shown by acetaminophen absorption test. Comp Clin Pathol 2017;27:283–287.
    doi: 10.1007/s00580-017-2585-1google scholar: lookup
  57. Moore JN, Hardee MM, Hardee GE. Modulation of arachidonic acid metabolism in endotoxic horses: comparison of flunixin meglumine, phenylbutazone, and a selective thromboxane synthetase inhibitor. Am J Vet Res 1986;47(1):110–113.
  58. Jibril F, Sharaby S, Mohamed A, Wilby KJ. Intravenous versus oral acetaminophen for pain: systematic review of current evidence to support clinical decision‐making. Can J Hosp Pharm 2015;68(3):238–247.
    doi: 10.4212/cjhp.v68i3.1458google scholar: lookup
  59. Ishikawa Y, Sakai DM, Im JS, Zhang S, Reed RA, Quandt JE. Antinociceptive effects of bupivacaine injected within the internal abdominis rectus sheath in standing healthy horses. Vet Anaesth Analg 2023;50(3):294–301.
    doi: 10.1016/j.vaa.2023.02.013google scholar: lookup
  60. Oscier CD, Milner QJW. Peri‐operative use of paracetamol. Anaesthesia 2009;64(1):65–72.
    doi: 10.1111/j.1365-2044.2008.05674.xgoogle scholar: lookup
  61. Haddaway NR, Collins AM, Coughlin D, Kirk S. The role of Google scholar in evidence reviews and its applicability to grey literature searching. PLoS One 2015;10(9):e0138237.
    doi: 10.1371/journal.pone.0138237google scholar: lookup

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