Pharmacokinetics and thermal anti-nociceptive effects of oral morphine in horses.
Abstract: Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of single and multiple oral doses of morphine were assessed. Unassigned: Six horses received a single 0.2 mg/kg IV dose of morphine and multiple oral doses of 0.8 mg/kg morphine every 12 h for 4.5 days. Blood samples were collected throughout administration, morphine, and metabolite concentrations determined and pharmacokinetic analysis performed. Drug related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. Unassigned: The maximum concentrations of M6G were higher following oral administration compared to IV and the combined morphine and M6G concentrations exceeded that of IV administration starting at 2 h. Oral administration of 0.8 mg/kg morphine provided and maintained comparable anti-nociception effects to IV morphine with less adverse effects, following single and multiple doses. Morphine was well tolerated following oral administration with less excitation and minimal effects on gastrointestinal borborygmi scores compared to IV administration. Unassigned: Results of the current study warrant further investigation of the anti-nociceptive effects of oral morphine administration to horses.
Copyright © 2024 Knych, Steinmetz, Traynham, McKemie and Kass.
Publication Date: 2024-09-17 PubMed ID: 39355143PubMed Central: PMC11443510DOI: 10.3389/fvets.2024.1461648Google Scholar: Lookup
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- Journal Article
Summary
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This research investigates the pharmacokinetics and analgesic effects of oral morphine in horses and shows that oral administration of morphine is effective and has fewer side effects compared to intravenous administration.
Introduction
- The article starts by stating the primary purpose of the study: to assess the analgesic effects and pharmacokinetics of oral morphine administration in horses. It provides a background where it mentions that although morphine is an effective analgesic for horses, its intravenous administration can lead to undesirable side effects like neuroexcitation and gastrointestinal issues.
- The article also explains that a metabolite of morphine, morphine-6-glucuronide (M6G), is partly responsible for the pain relief property of morphine. The researchers were looking to observe if oral administration produces comparable M6G levels as intravenous administration, but without the adverse effects.
Methods
- In this study, six horses were used as subjects. A single 0.2 mg/kg intravenous dose of morphine was given, and then multiple oral doses of 0.8 mg/kg morphine were administered every 12 hours for 4.5 days.
- Blood samples were collected throughout this period. The concentration of morphine and its metabolites was determined, and a pharmacokinetic analysis was performed. Observations were also made on the horses’ behavior and physiological responses.
- Anti-nociceptive effects were assessed by application of heat and monitoring for thermal threshold latency in response to the stimuli.
Results
- The results show that the maximum concentrations of M6G were higher following oral administration compared to intravenous administration. Also, the combined concentrations of morphine and M6G exceeded that after intravenous administration, starting at 2 hours.
- The study suggests that oral administration of 0.8 mg/kg morphine provided comparable pain relief to intravenous morphine, with fewer adverse effects, after single and multiple doses.
- The reaction of the horses to oral administration of morphine was positive, with lesser excitation and minimal effects on gastrointestinal scores compared to intravenous administration.
Conclusion
- The conclusion drawn from the study is that the results warrant further investigation of the pain-relief effects of oral morphine administration to horses.
Cite This Article
APA
Knych HK, Steinmetz SJ, Traynham ML, McKemie DS, Kass PH.
(2024).
Pharmacokinetics and thermal anti-nociceptive effects of oral morphine in horses.
Front Vet Sci, 11, 1461648.
https://doi.org/10.3389/fvets.2024.1461648 Publication
Researcher Affiliations
- K.L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
- K.L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
- K.L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
- K.L. Maddy Equine Analytical Chemistry Laboratory (Pharmacology Section), School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
- Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Conflict of Interest Statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared HS was an editorial member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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