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Journal of veterinary pharmacology and therapeutics2023; 46(5); 311-325; doi: 10.1111/jvp.13126

Pharmacokinetics and effects of codeine in combination with acetaminophen on thermal nociception in horses.

Abstract: Codeine and acetaminophen in combination have proven to be an effective analgesic treatment for moderate-to-severe and postoperative pain in humans. Studies have demonstrated that codeine and acetaminophen, when administered as sole agents, are well tolerated by horses. In the current study, we hypothesized that administration of the combination of codeine and acetaminophen would result in a significant thermal antinociceptive effect compared with administration of either alone. Six horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and codeine plus acetaminophen (1.2 mg/kg codeine and 6-6.4 mg/kg acetaminophen) in a three-way balanced crossover design. Plasma samples were collected, concentrations of drug and metabolites determined via liquid chromatography-mass spectrometry, and pharmacokinetic analyses were performed. Pharmacodynamic outcomes, including effect on thermal thresholds, were assessed. Codeine C and AUC were significantly different between the codeine and combination group. There was considerable inter-individual variation in the pharmacokinetic parameters for codeine, acetaminophen, and their metabolites in horses. All treatments were well tolerated with minimal significant adverse effects. An increase in the thermal threshold was noted at 1.5 and 2 h, from 15 min through 6 h and 0.5, 1, 1.5, and 3 h in the codeine, acetaminophen, and combination groups, respectively.
© 2023 John Wiley & Sons Ltd.
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Publication Date: 2023-04-06 PubMed ID: 37021661DOI: 10.1111/jvp.13126Google 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.

The research investigates the impact of combined codeine and acetaminophen administration on thermal pain response in horses, comparing it to the administration of either drug individually. The findings suggest that the combination of codeine and acetaminophen has potential as an effective pain reliever in horses.

Research Design and Methodology

  • The research was conducted on six horses, and it adopted a three-way balanced crossover design.
  • The horses were administered oral doses of codeine (1.2 mg/kg), acetaminophen (20 mg/kg), and a combination of codeine and acetaminophen (1.2 mg/kg codeine and 6-6.4 mg/kg acetaminophen).
  • Plasma samples were taken, and the concentration levels of administered drugs and their metabolites were determined using liquid chromatography-mass spectrometry.

Pharmacokinetic and Pharmacodynamics Analysis

  • The researchers carried out pharmacokinetic analyses to understand how the horses’ bodies absorbed, distributed, metabolized, and excreted the drugs.
  • Pharmacodynamic outcomes were also assessed. Pharmacodynamics refers to the effects and mechanisms of action of a drug within the body.
  • Particularly, the effects of the drugs on thermal thresholds were monitored. This involved understanding the thermal pain responses of the horses.

Results and Findings

  • Results showed that significant differences in the concentration of codeine and the area under the drug concentration-time curve (codeine C and AUC) between the horses administered with codeine only and those given the drug combination.
  • Significant variation was observed in how different horses metabolized codeine, acetaminophen, and their metabolites. This inter-individual variation reveals the different metabolic responses of the horses to the same drugs.
  • No significant adverse effects were reported in all the treatments, indicating that both drugs and their combination were well tolerated by the horses.
  • The thermal pain response increased at varying time intervals in horses administered with codeine, acetaminophen, and their combination. The combination group showed increased thermal threshold at 1, 1.5, and 3 hours after drug administration.

The implications of this research may extend to developing effective analgesic treatments for moderate-to-severe and postoperative pain in horses, utilizing the combination of codeine and acetaminophen.

Cite This Article

APA
Tueshaus T, McKemie DS, Kanarr K, Kass PH, Knych HK. (2023). Pharmacokinetics and effects of codeine in combination with acetaminophen on thermal nociception in horses. J Vet Pharmacol Ther, 46(5), 311-325. https://doi.org/10.1111/jvp.13126

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 46
Issue: 5
Pages: 311-325

Researcher Affiliations

Tueshaus, Tisa
  • K.L Maddy Equine Analytical Pharmacology Laboratory, University of California Davis, School of Veterinary Medicine, Davis, California, USA.
McKemie, Daniel S
  • K.L Maddy Equine Analytical Pharmacology Laboratory, University of California Davis, School of Veterinary Medicine, Davis, California, USA.
Kanarr, Kirsten
  • K.L Maddy Equine Analytical Pharmacology Laboratory, University of California Davis, School of Veterinary Medicine, Davis, California, USA.
Kass, Philip H
  • Department of Medicine and Epidemiology, University of California Davis, School of Veterinary Medicine, Davis, California, USA.
Knych, Heather K
  • K.L Maddy Equine Analytical Pharmacology Laboratory, University of California Davis, School of Veterinary Medicine, Davis, California, USA.
  • Department of Molecular Biosciences, University of California Davis, School of Veterinary Medicine, Davis, California, USA.

MeSH Terms

  • Humans
  • Horses
  • Animals
  • Acetaminophen / therapeutic use
  • Nociception
  • Drug Therapy, Combination / veterinary
  • Codeine / therapeutic use
  • Codeine / adverse effects
  • Analgesics / therapeutic use
  • Pain, Postoperative / drug therapy
  • Pain, Postoperative / veterinary
  • Drug Combinations
  • Double-Blind Method
  • Horse Diseases / drug therapy

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