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Acta Vet Scand. 2019 Jun 20;61(1):28. doi: 10.1186/s13028-019-0464-2.

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

Author information

1
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.
2
Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA), 751 89, Uppsala, Sweden.
3
Department of Medicinal Chemistry, Faculty of Pharmacy, Uppsala University, Box 574, 751 23, Uppsala, Sweden.
4
Romerike Hesteklinikk, Riisveien 75, 2007, Kjeller, Norway.
5
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.
6
Department of Veterinary Clinical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Dyrlægevej 16, 1870, Copenhagen, Frederiksberg C, Denmark.
7
Department of Anatomy, Physiology and Biochemistry, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Box 7011, 750 07, Uppsala, Sweden.
8
Rikstotoklinikken Bjerke AS., Postboks 194, 0510, Oslo, Norway.
9
Production Animal Clinical Science, Faculty for Veterinary Medicine, The Norwegian University of Life Sciences, Box 369 sentrum, 0102, Oslo, Norway.

Abstract

BACKGROUND:

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.

KEYWORDS:

Corticosteroids; Pharmacodynamics; Pharmacokinetics; Quantitative pharmacology

PMID:
31221173
PMCID:
PMC6585085
DOI:
10.1186/s13028-019-0464-2
[Indexed for MEDLINE]
Free PMC Article

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