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Home / Equine Research Bank / BMC Vet Res / Pharmacokinetics, adverse effects and effects on thermal noc...
BMC veterinary research2022; 18(1); 196; doi: 10.1186/s12917-022-03299-0

Pharmacokinetics, adverse effects and effects on thermal nociception following administration of three doses of codeine to horses.

Abstract: In humans, codeine is a commonly prescribed analgesic that produces its therapeutic effect largely through metabolism to morphine. In some species, analgesic effects of morphine have also been attributed to the morphine-6-glucuronide (M6G) metabolite. Although an effective analgesic, administration of morphine to horses produces dose-dependent neuroexcitation at therapeutic doses. Oral administration of codeine at a dose of 0.6 mg/kg has been shown to generate morphine and M6G concentrations comparable to that observed following administration of clinically effective doses of morphine, without the concomitant adverse effects observed with morphine administration. Based on these results, it was hypothesized that codeine administration would provide effective analgesia with decreased adverse excitatory effects compared to morphine. Seven horses received a single oral dose of saline or 0.3, 0.6 or 1.2 mg/kg codeine or 0.2 mg/kg morphine IV (positive control) in a randomized balanced 5-way cross-over design. Blood samples were collected up to 72 hours post administration, codeine, codeine 6-glucuronide, norcodeine morphine, morphine 3-glucuronide and M6G concentrations determined by liquid chromatography- mass spectrometry and pharmacokinetic analysis performed. Pre- and post-drug related behavior, locomotor activity, heart rate and gastrointestinal borborygmi were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency. Results: Morphine concentrations were highest in the morphine dose group at all times post administration, however, M6G concentrations were significantly higher in all the codeine dose groups compared to the morphine group starting at 1 hour post drug administration and up to 72-hours in the 1.2 mg/kg group. With the exception of one horse that exhibited signs of colic following administration of 0.3 and 0.6 mg/kg, codeine administration was well tolerated. Morphine administration, led to signs of agitation, tremors and excitation. There was not a significant effect on thermal nociception in any of the dose groups studied. Conclusions: The current study describes the metabolic profile and pharmacokinetics of codeine in horses and provides information that can be utilized in the design of future studies to understand the anti-nociceptive and analgesic effects of opioids in this species with the goal of promoting judicious and safe use of this important class of drugs.
© 2022. The Author(s).
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Publication Date: 2022-05-25 PubMed ID: 35614473PubMed Central: PMC9131543DOI: 10.1186/s12917-022-03299-0Google Scholar: Lookup
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  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

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 effects of various doses of codeine, a commonly used painkiller, on horses. The study aimed to prove that administering codeine could provide effective pain relief with fewer side effects compared to morphine.

Methodology

  • Seven horses were given different treatments: saline, three doses of codeine (0.3, 0.6, and 1.2 mg/kg), and morphine (0.2 mg/kg) for comparison. This process was carried out in a randomized and balanced design, which ensured each horse was subjected to different conditions in a certain order.
  • After the drug administration, blood samples were taken until 72 hours post administration. The samples were used to determine the amounts of codeine, its derivatives, and morphine metabolites in the blood, using a technique called liquid chromatography-mass spectrometry.
  • Several indicators of the horses’ conditions were recorded, such as their behavior, movement activity, heart rate, and gastrointestinal sounds. The researchers also tested for the horses’ sensitivity to pain by measuring thermal threshold latency.

Results

  • The morphine concentrations in the blood were highest in the group that received the morphine dose. Nevertheless, the concentrations of a morphine-like metabolite (M6G) were significantly higher in all codeine groups than in the morphine group, starting one hour after drug administration and up to 72 hours in the group that received the highest dose of codeine (1.2 mg/kg).
  • The administration of codeine was well-tolerated, with only one horse showing signs of colic after receiving the lower doses of codeine (0.3 and 0.6 mg/kg). On the other hand, administration of morphine led to agitation, tremors, and excitement in horses.
  • It was also found that there was no significant effect on thermal nociception (the horses’ response to potentially harmful heat stimuli) in any of the dose groups studied.

Conclusions

  • The results provide useful insights into the metabolic profile and pharmacokinetics of codeine in horses. The findings could be instrumental in designing future studies on the pain-relieving effects of opioids in horses, with the ultimate goal of promoting the judicious and safe use of this essential drug class.
  • Despite the promising findings, the lack of significant effect on thermal nociception across all dose groups suggests that more extensive studies are necessary to fully understand the analgesic capabilities of codeine in the equine species.

Cite This Article

APA
Knych HK, Stucker K, Gretler SR, Kass PH, McKemie DS. (2022). Pharmacokinetics, adverse effects and effects on thermal nociception following administration of three doses of codeine to horses. BMC Vet Res, 18(1), 196. https://doi.org/10.1186/s12917-022-03299-0

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 18
Issue: 1
Pages: 196

Researcher Affiliations

Knych, Heather K
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA. hkknych@ucdavis.edu.
  • Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA. hkknych@ucdavis.edu.
Stucker, Kristen
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
Gretler, Sophie R
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.
Kass, Philip H
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, USA.
McKemie, Daniel S
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, CA, 95616, USA.

MeSH Terms

  • Analgesics, Opioid
  • Animals
  • Codeine / adverse effects
  • Codeine / pharmacokinetics
  • Glucuronides / adverse effects
  • Glucuronides / pharmacokinetics
  • Horses
  • Morphine
  • Morphine Derivatives / adverse effects
  • Morphine Derivatives / pharmacokinetics
  • Nociception

Conflict of Interest Statement

Philip Kass is a member of the BMC Veterinary Research Editorial Board (Associate Editor). No other authors have any competing interests or declarations.

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Citations

This article has been cited 2 times.
  1. Blum S, Gisler J, Dalla Costa E, Montavon S, Spadavecchia C. Investigating conditioned pain modulation in horses: can the lip-twitch be used as a conditioning stimulus?. Front Pain Res (Lausanne) 2024;5:1463688.
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  2. Scantamburlo G, Nofziger C, Paulmichl M, Vanoni S. Genetic analysis of the equine orthologues for human CYP2D6: unraveling the complexity of the CYP2D family in horses. Front Vet Sci 2023;10:1188633.
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