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Home / Equine Research Bank / Acta Vet Scand / Disposition and effect of intra-articularly administered dex...
Acta veterinaria Scandinavica2019; 61(1); 28; doi: 10.1186/s13028-019-0464-2

Disposition and effect of intra-articularly administered dexamethasone on lipopolysaccharide induced equine synovitis.

Abstract: Dexamethasone is used for the intra-articular route of administration in management of aseptic arthritis in horses. Despite its widespread use there is very little quantitative data of the disposition and response to dexamethasone. The aim of this study was to investigate and describe the synovial fluid and plasma dexamethasone concentration over time and to explore the relation between synovial fluid concentration and response using clinical endpoints as response biomarkers after IA injection of dexamethasone disodium salt solution in an equine model of synovitis. Results: Inflammation was induced in the radiocarpal joint of six horses by injection of 2 ng lipopolysaccharide (LPS). Two hours later either saline or dexamethasone was injected in the same joint in a two treatment cross over design. Each horse was treated once with one of the six doses dexamethasone used (0.01, 0.03, 0.1, 0.3, 1 or 3 mg) and once with saline. Dexamethasone was quantified by means of UHPLC-MS/MS. Dexamethasone disposition was characterised by means of a non-linear mixed effects model. Lameness was evaluated both objectively with an inertial sensor based system and subjectively scored using a numerical scale (0-5). Joint circumference, skin temperature over the joint and rectal temperature were also recorded. The LPS-challenge induced lameness in all horses with high inter-individual variability. Dexamethasone significantly decreased lameness compared with saline. Other variables were not statistically significant different between treatments. Objective lameness scoring was the most sensitive method used in this study to evaluate the lameness response. A pharmacokinetic/pharmacodynamic model was successfully fitted to experimental dexamethasone and lameness data. The model allowed characterization of the dexamethasone synovial fluid concentration-time course, the systemic exposure to dexamethasone after intra-articular administration and the concentration-response relation in an experimental model of synovitis. Conclusions: The quantitative data improve the understanding of the pharmacology of dexamethasone and might serve as input for future experiments and possibly contribute to maintain integrity of equine sports.
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Publication Date: 2019-06-20 PubMed ID: 31221173PubMed Central: PMC6585085DOI: 10.1186/s13028-019-0464-2Google 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 aimed to understand the effects of intra-articular dexamethasone on synovitis (joint inflammation) in horses, identifying its concentration over time in synovial fluid and plasma. By studying this along with physiological changes, the research hopes to refine the clinical application of dexamethasone in equine medicine.

Objective and Methodology

  • The study was conducted to gather quantitative data about the administration of dexamethasone, a drug used to manage aseptic arthritis in horses, and its disposition and response within the body.
  • An equine model of synovitis was prepared, where inflammation was induced in the radiocarpal joint of six horses using a 2 ng lipopolysaccharide (LPS) injection.
  • Two hours post the LPS injection, either saline or one of six different doses of dexamethasone was administered in the inflamed joint.
  • Dexamethasone concentration in the synovial fluid and plasma was monitored over time.

Measurements and Results

  • Lameness, a clinical feature of synovitis, was measured both objectively via an inertial sensor-based system and subjectively using a numerical scale.
  • Other parameters such as joint circumference, skin temperature over the joint, and rectal temperature were also recorded to monitor the physiological changes.
  • The LPS-induced synovitis caused lameness in all horses with a significant degree of variability amongst individual horses.
  • Dexamethasone demonstrated a significant reduction in lameness compared to saline, affirming its anti-inflammatory properties.
  • However, other recorded variables didn’t show a statistically significant difference between the dexamethasone and saline treatments.

Outcome and Implication

  • The data generated was evaluated with a pharmacokinetic/pharmacodynamic model, enabling the researchers to characterize the behavior of dexamethasone in the synovial fluid over time, the systemic exposure to it following intra-articular administration, and the association between its concentration and response in synovitis.
  • This research provides valuable quantitative data that enhance our understanding of dexamethasone’s pharmacology.
  • The findings may benefit future experiments on this drug’s use and contribute towards maintaining the integrity of equine sports by improving equine arthritis management.

Cite This Article

APA
Ekstrand C, Bondesson U, Giving E, Hedeland M, Ingvast-Larsson C, Jacobsen S, Löfgren M, Moen L, Rhodin M, Saetra T, Ranheim B. (2019). Disposition and effect of intra-articularly administered dexamethasone on lipopolysaccharide induced equine synovitis. Acta Vet Scand, 61(1), 28. https://doi.org/10.1186/s13028-019-0464-2

Publication

Acta veterinaria Scandinavica
ISSN: 1751-0147
NlmUniqueID: 0370400
Country: England
Language: English
Volume: 61
Issue: 1
Pages: 28
PII: 28

Researcher Affiliations

Ekstrand, Carl
  • Department of Biomedical Sciences and Veterinary Public Health, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Box 7058, 750 07, Uppsala, Sweden. carl.ekstrand@slu.se.
Bondesson, Ulf
  • Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA), 751 89, Uppsala, Sweden.
  • Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University, Box 574, 751 23, Uppsala, Sweden.
Giving, Ellen
  • Romerike Hesteklinikk, Riisveien 75, 2007, Kjeller, Norway.
Hedeland, Mikael
  • Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA), 751 89, Uppsala, Sweden.
  • Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University, Box 574, 751 23, Uppsala, Sweden.
Ingvast-Larsson, Carina
  • Department of Biomedical Sciences and Veterinary Public Health, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Box 7058, 750 07, Uppsala, Sweden.
Jacobsen, Stine
  • Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlægevej 16, 1870, Copenhagen, Frederiksberg C, Denmark.
Löfgren, Maria
  • Department of Biomedical Sciences and Veterinary Public Health, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Box 7058, 750 07, Uppsala, Sweden.
Moen, Lars
  • Romerike Hesteklinikk, Riisveien 75, 2007, Kjeller, Norway.
Rhodin, Marie
  • Department of Anatomy, Physiology and Biochemistry, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Box 7011, 750 07, Uppsala, Sweden.
Saetra, Tonje
  • Rikstotoklinikken Bjerke AS., Postboks 194, 0510, Oslo, Norway.
Ranheim, Birgit
  • Production Animal Clinical Science, Faculty for Veterinary Medicine, The Norwegian University of Life Sciences, Box 369 sentrum, 0102, Oslo, Norway.

MeSH Terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacokinetics
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacokinetics
  • Horse Diseases / chemically induced
  • Horse Diseases / drug therapy
  • Horses
  • Injections, Intra-Articular / veterinary
  • Lipopolysaccharides
  • Synovitis / chemically induced
  • Synovitis / drug therapy
  • Synovitis / veterinary

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 4 times.
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  4. Kim KH, Park TS, Cho BW, Kim TM. Nanoparticles from Equine Fetal Bone Marrow-Derived Cells Enhance the Survival of Injured Chondrocytes.. Animals (Basel) 2020 Sep 23;10(10).
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