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Equine veterinary journal2022; 55(5); 891-898; doi: 10.1111/evj.13903

Pharmacokinetics of single dose administration of three increasing doses of acetaminophen per os in 1-3-month-old foals.

Abstract: Acetaminophen is a common analgesic and antipyretic drug used in human medicine and might be an alternative to nonsteroidal anti-inflammatory drugs for treating pain and pyrexia in foals. The pharmacokinetics and safety of differing doses of acetaminophen have not been investigated in foals. Objective: To determine the plasma pharmacokinetics and any changes in haematology and biochemistry profiles following oral administration of single doses of acetaminophen at 10, 20, and 40 mg/kg to foals. Methods: Randomised cross-over pharmacokinetic study. Methods: Six Quarter Horse (two colts and four fillies) foals received 10, 20, and 40 mg/kg acetaminophen orally once. Haematology and biochemistry profiles were performed before and 7 days after each drug administration. Blood samples were collected over 64 h after drug administration and were used to quantify plasma acetaminophen concentrations by liquid chromatography. Pharmacokinetic parameters were determined using compartmental analysis. Results: Median (range) acetaminophen plasma concentrations were 4.4 (1.8-5.1), 6.3 (2.6-12.6), and 14 (7.3-18) μg/ml for the 10, 20, and 40 mg/kg doses, respectively. Median acetaminophen area under the concentration versus time curve (AUC) ranged from 25 (11-32), 41 (22-74), and 105 (82-142) h × μg/ml for the 10, 20, and 40 mg/kg doses, respectively. Dose-normalised maximal concentrations and AUC values were similar across dose concentrations (p > 0.05). Median terminal half-life for all doses was 2.7-2.8 h. Haematology and biochemistry profiles were normal except for blood urea nitrogen and alkaline phosphatase concentrations. Conclusions: Foals were growing throughout the study, starting at 1 month and ending at 3 months. Deposition of drugs changes with age. The sample size was small and only single doses were evaluated. No liver biopsies were performed. Conclusions: Plasma disposition of acetaminophen after a single oral dose of 10, 20, and 40 mg/kg to 1-3-month-old foals varies greatly with the dose. The analgesic and antipyretic effect in foals is unknown. Unassigned: L'acétaminophène est un médicament analgésique et antipyrétique utilisé communément en médecine humaine. Il pourrait représenter une alternative aux médicaments anti-inflammatoires non-stéroïdiens pour le traitement de la douleur et de la fièvre chez les poulains. La pharmacocinétique et la sécurité de différentes doses d'acétaminophène n'ont pas encore été investigués chez les poulains. Objective: Déterminer la pharmacocinétique et les modifications aux profils hématologique et biochimique suivant l'administration orale d'une dose singulière d'acétaminophène à 10, 20 ou 40 mg/kg chez des poulains. TYPE D'ÉTUDE: Étude de pharmacocinétique croisée aléatoire. MÉTHODES: Six chevaux Quarter Horse (2 poulains mâles et 4 femelles) ont reçu 10, 20 et 40 mg/kg d'acétaminophène oralement à une reprise. Les profils hématologique et biochimique ont été analysés avant et 7 jours suivant chaque administration. Les échantillons sanguins ont été récoltés plus de 64 heures après l'administration de la médication et ont été utilisés pour quantifier les concentrations plasmatiques d'acétaminophène par chromatographie liquide. Les paramètres pharmacocinétiques ont été déterminés par analyse compartimentale. RÉSULTATS: Les concentrations plasmatiques médianes d'acétaminophène étaient de 4.4 (1.8-5.1), 6.3 (2.6-12.6), et 14 (7.3-18 ug/mL) pour les doses de 10, 20 et 40 mg/kg respectivement. L'aire sous la courbe médiane pour la concentration versus le temps de l'acétaminophène était de 25 (11-32), 41 (22-74) et 105 (82-142)h*ug/mL pour les doses de 10, 20 et 40 mg/kg respectivement. Les concentrations maximales à doses normalisées et les valeurs AUC étaient similaires entre les concentrations des doses (p < 0.05). La demi-vie terminale médiane pour toutes les doses était 2.7-2.8 heures. Les profils hématologique et biochimique étaient normaux, à l'exception des concentrations d'azote uréique sanguine et de phosphatase alcaline. Unassigned: Les poulains ont grandi durant l'étude, débutant à 1 mois et se terminant à 3 mois d'âge. La déposition des médicaments varie avec l'âge. La taille de l'échantillon était petit et des doses singulières seulement ont été évaluées. Aucune biopsie de foie n'a été recueillie. Conclusions: Le sort plasmatique de l'acétaminophène suivant une dose singulière de 10, 20 ou 40 mg/kg chez des poulains de 1-3 mois d'âge varie grandement selon la dose. Les effets analgésique et antipyrétique de l'acétaminophène chez les poulains demeurent inconnus.
© 2022 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2022-12-23 PubMed ID: 36482786DOI: 10.1111/evj.13903Google Scholar: Lookup
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Summary

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This study investigates the pharmacokinetics – how a drug is absorbed, distributed, metabolized, and excreted by the body – and safety profile of varying doses of acetaminophen in 1-3 month old foals. Administered orally at 10, 20, and 40mg/kg doses, acetaminophen’s efficacy as a potential alternative to nonsteroidal anti-inflammatory drugs for foals was explored, noting significant variance in plasma disposition of the drug based on dosage. The drug’s analgesic and antipyretic impact on foals, however, remains unestablished.

Procedure and Participants

  • The study was conducted as a randomized cross-over pharmacokinetic methodology, involving a sample group of six Quarter Horse foals – two male (colts) and four female (fillies).
  • A single oral administration of acetaminophen was given in dosages of 10, 20, and 40 mg/kg. Haematology and biochemistry profiles were evaluated before and after seven days of each drug administration.
  • Blood samples were gathered over a 64 hour period following the drug administration for further analysis.

Data Analysis Methods

  • Plasma acetaminophen concentrations were measured through liquid chromatography, a method used to separate and analyse compounds.
  • The study performed a compartmental analysis to determine pharmacokinetic parameters. This helps to understand how the drug moves within different bodily compartments over time.
  • Statistical analyses performed included the evaluation of median plasma concentrations, Acetaminophen area under the concentration versus time curve (AUC), and median terminal half-life for all doses. Comparisons were made across dosage concentrations.

Results and Conclusions

  • Significant variation was seen in plasma acetaminophen across different dosage levels, indicating that the drug’s plasma disposition in foals is heavily dose-dependent.
  • Medians of the plasma concentration and AUC consistently grew with the dosage size. However, dose-normalised maximum concentrations and AUC values were statistically similar.
  • The terminal half-life for all doses ranged from 2.7 to 2.8 hours, presenting consistent pharmacokinetic behaviour at different dosages.
  • With the exception of blood urea nitrogen and alkaline phosphatase concentrations, haematology and biochemistry profiles remained within normal ranges, suggesting the oral administration of single doses to be safe.
  • One limitation noted by the researchers was that the foals were growing throughout the study (from 1 to 3 months old), which could have influenced the deposition of drugs. The researchers concluded that while pharmacokinetics for single-dose administration were clear, the analgesic and antipyretic effects of acetaminophen in foals remain uncertain.

Cite This Article

APA
Gold JR, Grubb T, Court M, Villarino NF. (2022). Pharmacokinetics of single dose administration of three increasing doses of acetaminophen per os in 1-3-month-old foals. Equine Vet J, 55(5), 891-898. https://doi.org/10.1111/evj.13903

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English
Volume: 55
Issue: 5
Pages: 891-898

Researcher Affiliations

Gold, Jenifer Robin
  • Associate-Internal Medicine and Criticalist, Wisconsin Equine Clinic and Hospital, Oconomowoc, Wisconsin, USA.
Grubb, Tamara
  • Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington, USA.
Court, Michael
  • Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington, USA.
Villarino, Nicolas Francisco
  • Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington, USA.

MeSH Terms

  • Male
  • Animals
  • Humans
  • Horses
  • Female
  • Acetaminophen
  • Half-Life
  • Chromatography, Liquid / veterinary
  • Area Under Curve
  • Administration, Oral

Grant Funding

  • WSU Intramural Funding-Luella Gottstein Endowment for Equine Research
  • Stanley L. Alder Research Fund

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Citations

This article has been cited 1 times.
  1. 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
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