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Equine veterinary journal2022; doi: 10.1111/evj.13912

Morphine in donkeys: Antinociceptive effect and preliminary pharmacokinetics.

Abstract: Morphine is the prototypical μ-opioid receptor agonist used to provide analgesia in veterinary species. Its effects are well-described in horses but not donkeys. Objective: To determine the antinociceptive effects of two doses of morphine in donkeys. To describe preliminary pharmacokinetic parameters of morphine in donkeys. Methods: In vivo experiment. Methods: Eight adult castrated male donkeys were given intravenous (IV) 0.9% saline, morphine 0.1 mg/kg bwt (LDM), or morphine 0.5 mg/kg bwt (HDM) in a randomised order with a minimum 1-week washout period. Mechanical nociceptive thresholds (MNTs) were determined by a blinded investigator pre-injection and 15, 30, 45, 60, 90, 120, 150, 180, 210, 240, 300, and 360 min post-injection. Venous blood samples were collected pre-injection and 2, 5, 10, 15, 30, 45, 60, 90, and 120 min post-injection. Data were analysed using Friedman's test with Dunn's post hoc test for multiple comparisons. Pharmacokinetic parameters were calculated for the HDM treatment. Results: Baseline MNT was [median (interquartile range)] 8.9 (7.1-10.3) N and did not differ between treatments. Peak MNTs occurred at 60 min for both LDM (16.2 N) and HDM (25.0 N) treatments. MNTs after HDM treatment were higher than saline (p < 0.04) at 15, 60, 90, 120, 150, 180, 240, and 300 min post-injection. MNTs after LDM treatment were higher than baseline (p < 0.05) at 45 and 60 min post-injection. Terminal half-life for HDM was (mean ± SD) 51.0 ± 10.7 min, the volume of distribution at steady-state 2.07 ± 0.33 L/min and clearance 49.2 ± 4.16 ml * min/kg using noncompartmental analysis. The concentration of morphine-3-glucuronide (M3G) was higher than morphine-6-glucuronide (M6G) at all sampled time points. Conclusions: Short duration of plasma sampling for pharmacokinetic analysis; lack of objective measure of gastrointestinal function. Conclusions: The HDM treatment provided mechanical antinociception in donkeys with no significant adverse effects.
© 2022 EVJ Ltd.
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Publication Date: 2022-12-20 PubMed ID: 36537849DOI: 10.1111/evj.13912Google 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 study investigated the pain-relieving effects and preliminary pharmacokinetics (the movement of drugs within the body) of two different doses of morphine in adult male donkeys. The study found that the higher dose of morphine provided significant pain relief without any significant adverse effects.

Objectives and Methodology

  • The study aimed to explore the pain-relieving, or antinociceptive, effects of two doses of morphine in adult male donkeys.
  • The secondary objective was to explore the pharmacokinetics of morphine in donkeys, which refers to how the drug is absorbed, distributed, metabolized, and excreted in the body.
  • Eight adult castrated male donkeys were given intravenous solutions of saline, low-dose morphine, or high-dose morphine in a randomized order, with a minimum period of one week in between each administration (known as a washout period).
  • Pain thresholds were measured at various time intervals post-injection, and blood samples were also collected to observe the presence and behavior of morphine in the blood.

Findings

  • Peak pain thresholds occurred 60 minutes after both low- and high-dose morphine treatments, indicating the most pronounced pain relief effect at this point.
  • The pain thresholds after high-dose morphine treatment were significantly higher than saline at several time points post-injection, demonstrating the effectiveness of the high-dose morphine.
  • The low-dose morphine treatment revealed an increase in pain thresholds at 45 and 60 minutes post-injection.
  • The higher dose of morphine had a terminal half-life of 51.0 minutes, which indicates the time it took for the amount of morphine in the body to decrease by half.
  • The analysis of morphine metabolites (breakdown products) showed higher concentration of morphine-3-glucuronide (M3G) than morphine-6-glucuronide (M6G) at all sampled time points.

Conclusions

  • The study concluded that the high-dose morphine treatment provided significant pain relief for donkeys without leading to any notable adverse effects.
  • However, it did note limitations including the short duration of plasma sampling for pharmacokinetic analysis and lack of objective measure of gastrointestinal function.

Cite This Article

APA
Maney JK, Dzikiti BT, Escobar A, Knych HK, Bennett RC. (2022). Morphine in donkeys: Antinociceptive effect and preliminary pharmacokinetics. Equine Vet J. https://doi.org/10.1111/evj.13912

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Maney, Jill K
  • Clinical Sciences Department, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.
Dzikiti, Brighton T
  • Clinical Sciences Department, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.
Escobar, Andre
  • Clinical Sciences Department, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.
Knych, Heather K
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
Bennett, Rachel C
  • AndersonMoores Veterinary Specialists, Winchester, UK.

Grant Funding

  • D20EQ-825 / Morris Animal Foundation

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