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Veterinary anaesthesia and analgesia2020; 47(5); 694-704; doi: 10.1016/j.vaa.2020.04.004

Metabolism, pharmacokinetics and selected pharmacodynamic effects of codeine following a single oral administration to horses.

Abstract: To describe the pharmacokinetics and selected pharmacodynamic variables of codeine and its metabolites in Thoroughbred horses following a single oral administration. Methods: Prospective experimental study. Methods: A total of 12 Thoroughbred horses, nine geldings and three mares, aged 4-8 years. Methods: Horses were administered codeine (0.6 mg kg) orally and blood was collected before administration and at various times until 120 hours post administration. Plasma and urine samples were collected and analyzed for codeine and its metabolites by liquid chromatography-mass spectrometry, and plasma pharmacokinetics were determined. Heart rate and rhythm, step counts, packed cell volume and total plasma protein were measured before and 4 hours after administration. Results: Codeine was rapidly converted to the metabolites norcodeine, codeine-6-glucuronide (C6G), morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Plasma codeine concentrations were best represented using a two-compartment model. The C t and elimination t were 270.7 ± 136.0 ng mL, 0.438 ± 0.156 hours and 2.00 ± 0.534 hours, respectively. M3G was the main metabolite detected (C 492.7 ± 35.5 ng mL), followed by C6G (C 96.1 ± 33.8 ng mL) and M6G (C 22.3 ± 4.96 ng mL). Morphine and norcodeine were the least abundant metabolites with C of 3.17 ± 0.95 and 1.42 ± 0.79 ng mL, respectively. No significant adverse or excitatory effects were observed. Conclusions: Following oral administration, codeine is rapidly metabolized to morphine, M3G, M6G, C6G and norcodeine in horses. Plasma concentrations of M6G, a presumed active metabolite of morphine, were comparable to concentrations reported previously following administration of an analgesic dose of morphine to horses. Codeine was well tolerated based on pharmacodynamic variables and behavioral observations.
Copyright © 2020 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.
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Publication Date: 2020-04-23 PubMed ID: 32654915PubMed Central: PMC7872472DOI: 10.1016/j.vaa.2020.04.004Google 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 study focuses on the metabolism, pharmacokinetics, and selected pharmacodynamic variables of Codeine in Thoroughbred horses following a single oral administration.

Research Methodology

  • The study recruited 12 Thoroughbred horses as test subjects, consisting of nine geldings and three mares, aged between 4-8 years.
  • Each horse was administered a single oral dose of Codeine.
  • Blood samples were collected at set intervals until 120 hours following the administration to monitor the behavior of the drug in the bloodstream.
  • Plasma and urine samples were then analyzed for the presence of Codeine and its metabolites using liquid chromatography-mass spectrometry, providing insight into the drug’s pharmacokinetics.
  • Various physiological measures, including heart rate, step counts, and packed cell volumes, were recorded before and 4 hours after Codeine administration to assess the drug’s pharmacodynamic effects.

Research Findings

  • Codeine was found to be rapidly metabolized into various compounds, including norcodeine, codeine-6-glucuronide (C6G), morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G).
  • The drug’s presence in the plasma was best represented by a two-compartment model, implying that it is distributed in more than one area of the body.
  • M3G was the primary metabolite detected, followed by C6G and M6G. Morphine and norcodeine recorded the least concentrations.
  • No significant adverse or excitatory effects were observed post-administration, demonstrating that Codeine was well-tolerated by the horses.

Research Conclusions

  • Codeine is quickly transformed into morphine, M3G, M6G, C6G and norcodeine following oral administration in horses.
  • The plasma concentrations of M6G, an assumed active metabolite of Morphine, were comparable to concentrations previously reported after analgesic doses of Morphine were administered to horses.
  • Based on both the physiological measures recorded and behavioral observations, Codeine was found to be well-tolerated by the horses.

Cite This Article

APA
Gretler SR, Finno CJ, McKemie DS, Kass PH, Knych HK. (2020). Metabolism, pharmacokinetics and selected pharmacodynamic effects of codeine following a single oral administration to horses. Vet Anaesth Analg, 47(5), 694-704. https://doi.org/10.1016/j.vaa.2020.04.004

Publication

Veterinary anaesthesia and analgesia
ISSN: 1467-2995
NlmUniqueID: 100956422
Country: United States
Language: English
Volume: 47
Issue: 5
Pages: 694-704
PII: S1467-2987(20)30083-0

Researcher Affiliations

Gretler, Sophie R
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, University of California-Davis, School of Veterinary Medicine, Davis, CA, USA.
Finno, Carrie J
  • 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, University of California-Davis, School of Veterinary Medicine, Davis, CA, USA.
Kass, Philip H
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA, USA.
Knych, Heather K
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, University of California-Davis, School of Veterinary Medicine, Davis, CA, USA; Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA. Electronic address: hkknych@ucdavis.edu.

MeSH Terms

  • Administration, Oral
  • Animals
  • Area Under Curve
  • Codeine / blood
  • Codeine / metabolism
  • Codeine / pharmacokinetics
  • Codeine / urine
  • Drug Administration Schedule
  • Female
  • Half-Life
  • Horses / metabolism
  • Male

Grant Funding

  • L40 TR001136 / NCATS NIH HHS

Conflict of Interest Statement

Conflict of interest statement. The authors declare no conflict of interest

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Citations

This article has been cited 2 times.
  1. Knych HK, Stucker K, Gretler SR, Kass PH, McKemie DS. Pharmacokinetics, adverse effects and effects on thermal nociception following administration of three doses of codeine to horses. BMC Vet Res 2022 May 25;18(1):196.
    doi: 10.1186/s12917-022-03299-0pubmed: 35614473google scholar: lookup
  2. Gretler SR, Finno CJ, Kass PH, Knych HK. Functional phenotyping of the CYP2D6 probe drug codeine in the horse. BMC Vet Res 2021 Feb 13;17(1):77.
    doi: 10.1186/s12917-021-02788-ypubmed: 33581736google scholar: lookup
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