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Home / Equine Research Bank / Can J Vet Res / Preliminary study of the pharmacokinetics, tissue distributi...
Canadian journal of veterinary research = Revue canadienne de recherche veterinaire2022; 86(3); 172-180;

Preliminary study of the pharmacokinetics, tissue distribution, and behavioral and select physiological effects of morphine 6-glucuronide (M6G) following intravenous administration to horses.

Abstract: Although morphine has demonstrated antinociceptive effects in horses, its administration has been associated with dose-dependent adverse effects. In humans and rats, part of the analgesic effect of morphine has been attributed to the active metabolite, morphine-6-glucuronide (M6G). Although morphine can cause several undesirable effects, M6G has a more favorable safety profile. The objective of this study was to characterize the pharmacokinetics, tissue distribution, and behavioral and select physiological effects of M6G following intravenous administration to a small group of horses. In Part 1 of the study, 3 horses received a single intravenous administration of saline, 0.5 mg/kg body weight (BW) M6G, or 0.5 mg/kg BW morphine in a 3-way crossover design. Blood samples were collected up to 96 hours post-administration, concentrations of drug and metabolites measured, and pharmacokinetics determined. Behavioral and physiological effects were then recorded. In Part 2 of the study, 2 horses scheduled to be euthanized for other reasons, were administered 0.5 mg/kg BW M6G. Blood, cerebrospinal fluid (CSF), and various tissue samples were collected post-administration and concentrations of drug were determined. The clearance of M6G was more rapid and the volume of distribution at steady state was smaller for M6G compared to morphine. A reaction characterized by head shaking, pawing, and slight ataxia was observed immediately following administration of both morphine and M6G to horses. After M6G administration, these behaviors subsided rapidly and were followed by a longer period of sedation. Following administration, M6G was detected in the kidney, liver, CSF, and regions of the brain. Results of this study encourage further investigation of M6G in order to assess its clinical feasibility as an analgesic in horses. Bien que la morphine ait démontré des effets antinociceptifs chez les chevaux, son administration a été associée avec des effets non-désirés d’une manière dose-dépendante. Chez les humains et les rats, une partie de l’effet analgésique de la morphine a été attribuée au métabolite actif, morphine-6-glucuronide (M6G). Bien que la morphine puisse causer plusieurs effets indésirables, M6G a un profil de sécurité plus favorable. L’objectif de cette étude était de caractériser la pharmacocinétique, la distribution tissulaire, et le comportement et sélectionner des effets physiologiques de M6G suivant son administration intraveineuse à un petit groupe de chevaux. Dans la Partie 1 de l’étude, trois chevaux ont reçu l’administration intraveineuse d’une dose unique de saline, 0,5 mg/kg de poids corporel (BW) de M6G, ou 0,5 mg/kg BW de morphine selon un essai croisé à trois voies. Des échantillons sanguins ont été prélevés jusqu’à 96 h post-administration, les concentrations de drogues et de métabolites mesurées, et les pharmacocinétiques déterminées. Les effets physiologiques et sur le comportement ont par la suite été notés. Dans la Partie 2 de l’étude, deux chevaux devant être euthanasiés pour d’autres raisons, ont reçu 0,5 mg/kg BW de M6G. Du sang, du liquide céphalo-rachidien (CSF), et différents échantillons de tissu ont été prélevés post-administration et les concentration de drogue furent déterminées. La clairance de M6G a été plus rapide et le volume de distribution à l’état d’équilibre était plus petit pour M6G comparativement à la morphine. Une réaction caractérisée par le tremblement de la tête, du piaffage, et une légère ataxie a été observée immédiatement à la suite de l’administration soit de morphine ou de M6G aux chevaux. Après administration de M6G, ces comportements diminuèrent rapidement et furent suivis par une période plus longue de sédation. À la suite de l’administration, M6G a été détecté dans les reins, le foie, le CSF, et des régions du cerveau. Les résultats de cette étude incitent à réaliser des études additionnelles sur M6G afin d’évaluer son potentiel clinique comme analgésique chez les chevaux.(Traduit par Docteur Serge Messier).
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Publication Date: 2022-07-08 PubMed ID: 35794968PubMed Central: PMC9251799
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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 aims to investigate the pharmacokinetics, tissue distribution, and behavioral and physiological effects of the pain-relieving drug morphine-6-glucuronide (M6G) in horses, with the hope it could offer a safer alternative to morphine.

Methodology and Design

  • The first part of the study observed three horses who received either saline, M6G, or morphine. This process allowed a proper comparison of the effects and metabolism of the different substances.
  • Blood samples were taken up to 96 hours after administration, with the concentrations of drug and metabolites assessed alongside their pharmacokinetic properties.
  • Behavioral and physiological effects were also recorded.
  • The second part focused on two horses which were to be euthanized for unrelated reasons. These horses were administered the same dosage of M6G and the concentrations of the drug were determined in blood, cerebrospinal fluid (CSF), and various tissue samples that were collected post-administration.

Findings

  • M6G cleared more quickly from the system compared to morphine, and its volume of distribution at a steady state was smaller compared to morphine.
  • Both morphine and M6G resulted in immediate reactions such as head shaking, pawing, and slight ataxia in horses. These behaviors quickly subsided following M6G administration and were followed by a relatively longer period of sedation.
  • M6G was detected in the kidney, liver, CSF, and regions of the brain after administration.

Implication of the Study

The results of this preliminary study indicate that M6G can be further investigated for potential use as an analgesic in horses. As M6G is believed to have a more favorable safety profile than morphine, it could be developed as an effective alternative for pain management in horses to avoid the undesirable side effects that are often associated with morphine use. However, more extensive research is needed to confirm its clinical feasibility and understand its long-term effects.

Cite This Article

APA
Hamamoto-Hardman BD, Steffey EP, Seminoff K, McKemie DS, Kass P, Knych HK. (2022). Preliminary study of the pharmacokinetics, tissue distribution, and behavioral and select physiological effects of morphine 6-glucuronide (M6G) following intravenous administration to horses. Can J Vet Res, 86(3), 172-180.

Publication

Canadian journal of veterinary research = Revue canadienne de recherche veterinaire
ISSN: 1928-9022
NlmUniqueID: 8607793
Country: Canada
Language: English
Volume: 86
Issue: 3
Pages: 172-180

Researcher Affiliations

Hamamoto-Hardman, Briana D
  • K.L. Maddy Equine Analytical Pharmacology Laboratory (Hamamoto-Hardman, Steffey, Seminoff, McKemie, Knych), Department of Veterinary Surgery and Radiology (Steffey), Department of Medicine and Epidemiology (Kass), and Department of Molecular Biosciences (Knych), School of Veterinary Medicine, University of California, 620 West Health Science Drive, Davis, California 95616, USA.
Steffey, Eugene P
  • K.L. Maddy Equine Analytical Pharmacology Laboratory (Hamamoto-Hardman, Steffey, Seminoff, McKemie, Knych), Department of Veterinary Surgery and Radiology (Steffey), Department of Medicine and Epidemiology (Kass), and Department of Molecular Biosciences (Knych), School of Veterinary Medicine, University of California, 620 West Health Science Drive, Davis, California 95616, USA.
Seminoff, Kelsey
  • K.L. Maddy Equine Analytical Pharmacology Laboratory (Hamamoto-Hardman, Steffey, Seminoff, McKemie, Knych), Department of Veterinary Surgery and Radiology (Steffey), Department of Medicine and Epidemiology (Kass), and Department of Molecular Biosciences (Knych), School of Veterinary Medicine, University of California, 620 West Health Science Drive, Davis, California 95616, USA.
McKemie, Daniel S
  • K.L. Maddy Equine Analytical Pharmacology Laboratory (Hamamoto-Hardman, Steffey, Seminoff, McKemie, Knych), Department of Veterinary Surgery and Radiology (Steffey), Department of Medicine and Epidemiology (Kass), and Department of Molecular Biosciences (Knych), School of Veterinary Medicine, University of California, 620 West Health Science Drive, Davis, California 95616, USA.
Kass, Philip
  • K.L. Maddy Equine Analytical Pharmacology Laboratory (Hamamoto-Hardman, Steffey, Seminoff, McKemie, Knych), Department of Veterinary Surgery and Radiology (Steffey), Department of Medicine and Epidemiology (Kass), and Department of Molecular Biosciences (Knych), School of Veterinary Medicine, University of California, 620 West Health Science Drive, Davis, California 95616, USA.
Knych, Heather K
  • K.L. Maddy Equine Analytical Pharmacology Laboratory (Hamamoto-Hardman, Steffey, Seminoff, McKemie, Knych), Department of Veterinary Surgery and Radiology (Steffey), Department of Medicine and Epidemiology (Kass), and Department of Molecular Biosciences (Knych), School of Veterinary Medicine, University of California, 620 West Health Science Drive, Davis, California 95616, USA.

MeSH Terms

  • Administration, Intravenous / veterinary
  • Analgesics, Opioid
  • Animals
  • Glucuronides
  • Horses
  • Morphine / pharmacology
  • Morphine Derivatives / pharmacokinetics
  • Rats
  • Tissue Distribution

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