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Journal of veterinary pharmacology and therapeutics2023; 46(4); 238-249; doi: 10.1111/jvp.13122

Concentrations, pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites following oral administration to horses.

Abstract: The metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been associated with neuroexcitation and adverse gastrointestinal effects. In this study, we hypothesized that oral administration would lead to comparable concentrations of morphine and its presumed active metabolite, morphine 6-glucuronide (M6G) without the adverse effects associated with i.v. administration. Eight horses were administered a single i.v. dose of 0.2 mg/kg morphine and oral doses of 0.2, 0.6, and 0.8 mg/kg of morphine in a four-way balanced crossover design, with a 2-week washout period between doses. Concentrations of morphine and metabolites were determined, and pharmacokinetic parameters determined. Physiologic and behavioral outcomes including the number of steps taken, changes in heart rate, and gastrointestinal borborygmi were assessed. Oral administration of morphine resulted in higher concentrations of morphine metabolites, including M6G (C : 11.6-37.8 ng/mL (0.6 mg/kg); 15.8-42.6 ng/mL (0.8 mg/kg)), compared with i.v. Bioavailability was 36.5%, 27.6% and 28.0% for 0.2, 0.6 and 0.8 mg/kg, respectively. Behavioral and physiologic changes were noted in all groups but were less prominent with oral compared with i.v. administration. Results of the current study are encouraging for further study, specifically anti-nociceptive effects of morphine following oral administration.
© 2023 John Wiley & Sons Ltd.
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Publication Date: 2023-03-08 PubMed ID: 36883679DOI: 10.1111/jvp.13122Google 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.

This research investigates how orally administering morphine to horses impacts the concentration of the drug and its active metabolites. It’s found that oral administration can lead to comparable drug concentrations to intravenous administration but with fewer adverse effects.

Study Design

The study followed a controlled and detailed setup. Here are the key elements of the experiment:

  • The researchers examined the effect of oral morphine administration on eight horses. They compared this with the effects of intravenous (i.v.) administration.
  • The horses were given a single i.v. dose of morphine measuring 0.2 mg/kg. Oral doses measuring 0.2, 0.6, and 0.8 mg/kg were also administered. The different drug administrations followed a four-way balanced crossover design, with a two-week washout period between each dose. This design ensures that each horse could serve as its own control, which helps minimize the influence of individual variations among the test subjects.
  • The concentrations of morphine and its metabolites were then measured and the pharmacokinetics or drug behavior within the body was determined.
  • The researchers also monitored changes in behaviors and physiological parameters such as heart rate, number of steps taken, and gastrointestinal sounds or ‘borborygmi’.

Findings

The research results provided notable insights into the effects of oral morphine administration in horses. Here are some of the primary findings:

  • Oral administration of morphine findings revealed higher concentrations of morphine metabolites, particularly M6G. The concentrations ranged from 11.6-37.8 ng/mL for a 0.6 mg/kg dose and 15.8-42.6 ng/mL for a 0.8 mg/kg dose.
  • The bioavailability of morphine, which refers to the proportion of drug that enters the circulation and could have an active effect, was found to be 36.5% for a 0.2 mg/kg dose, 27.6% for a 0.6 mg/kg dose and 28.0% for a 0.8 mg/kg dose. These rates indicate that a significant amount of the drug is absorbed and used by the body.
  • Behavioral and physiological changes were observed in the horses. But such changes were less prominent with oral administration compared to intravenous administration, suggesting that oral administration might cause fewer side effects.

Implications

The results of this study provide promising implications for future research and potential medical usage. The observation that oral administration of morphine can lead to comparable drug and metabolite concentrations as intravenous administration, but with fewer behavioral and physiological changes, implies it might be a preferable route of administration. This finding encourages further examination, specifically regarding the pain-relieving or ‘anti-nociceptive’ effects of morphine when administered orally.

Cite This Article

APA
Poth MKM, McKemie DS, Traynham M, Kass PH, Knych HK. (2023). Concentrations, pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites following oral administration to horses. J Vet Pharmacol Ther, 46(4), 238-249. https://doi.org/10.1111/jvp.13122

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 46
Issue: 4
Pages: 238-249

Researcher Affiliations

Poth, Meghan K M
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
McKemie, Daniel S
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Traynham, Megan
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Kass, Philip H
  • Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
Knych, Heather K
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
  • Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.

MeSH Terms

  • Animals
  • Administration, Oral
  • Analgesics, Opioid / pharmacology
  • Biological Availability
  • Horses
  • Morphine / pharmacology
  • Morphine Derivatives
  • Cross-Over Studies

Grant Funding

  • T35 OD010956 / ODCDC CDC HHS
  • T35 OD010956 / ODCDC CDC HHS

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Citations

This article has been cited 2 times.
  1. Karačonji IB, Jelača T, Jurič A, Vrdoljak AL. Morphine and codeine in racing horse feed: is there reason for concern?. Arh Hig Rada Toksikol 2025 Mar 1;76(1):60-66.
    doi: 10.2478/aiht-2025-76-3888pubmed: 40222175google scholar: lookup
  2. Knych HK, Steinmetz SJ, Traynham ML, McKemie DS, Kass PH. Pharmacokinetics and thermal anti-nociceptive effects of oral morphine in horses. Front Vet Sci 2024;11:1461648.
    doi: 10.3389/fvets.2024.1461648pubmed: 39355143google scholar: lookup
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