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Dexamethasone in horses

safe usage from an anti-doping and medication perspective

Ekstrand, Carl (2017). Dexamethasone in horses. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae, 1652-6880 ; 2017:31
ISBN 978-91-576-8835-4
eISBN 978-91-576-8836-1
[Doctoral thesis]

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Abstract

Equine athletes and companion horses are commonly treated with glucocorticoids such as dexamethasone. Care of sick or injured animals is vital for the animal welfare. To protect the integrity of equine sport, legal therapeutic substances are regulated during competition. The overall aim of this thesis was to provide quantitative information of dexamethasone exposure and response in Standardbreds and to relate this information to medication and anti-doping methodology.

Dexamethasone-21-isonicotinate suspension administered intramuscularly and dexamethasone sodium phosphate solution administered both intravenously and intra- articularly were used in experiments. Dexamethasone was quantified in plasma, urine and synovial fluid by means of UHPLC-MS/MS. Cortisol response, IL-1β response, joint circumference response, local skin temperature response and lameness response were used as biomarkers. Dexamethasone plasma- and synovial fluid concentration-time courses were characterised by means of compartment modelling. The response-time courses were described by fitting a turnover model with an inhibitory function to experimental biomarker response data.

Dexamethasone exposure was described in plasma and synovial fluid. In the Standardbreds studied, median dexamethasone plasma clearance was 0.51 L∙h-1∙kg-1 and median volume of distribution (at steady state) was 1.58 L∙kg-1. The median half-life in plasma and synovial fluid was 2.4 h and 1.3 h, respectively. After intramuscular administration of dexamethasone-21-isonicotinate, mean terminal half-life was 39 h due to slow release into plasma from the injection site. The dexamethasone concentration was 4- to 15-fold higher in urine than in plasma. A circadian cortisol baseline was described using a cosine function and cortisol response was characterised. Median potency value and for cortisol response in plasma was 0.039 ng∙mL-1 and the efficacy value was 0.92. Dexamethasone inhibited lameness and synovial fluid IL-1β release at doses lower than the approved. The median calculated synovial fluid concentration that suppressed lameness response by 50 % was 17 ng∙mL-1. The tentative potency value for IL-1β response was 19 ng∙mL-1.

The information provided in this thesis can be used to improve future medication protocols and anti-doping controls which could improve animal welfare.

Authors/Creators:Ekstrand, Carl
Title:Dexamethasone in horses
Subtitle:safe usage from an anti-doping and medication perspective
Series/Journal:Acta Universitatis agriculturae Sueciae (1652-6880)
Year of publishing :2017
Depositing date:16 March 2017
Volume:2017:31
Number of Pages:91
Papers/manuscripts:
NumberReferences
IEkstrand, C., Bondesson, U., Gabrielsson, J., Hedeland, M., Kallings, P., Olsén, L. & Ingvast-Larsson, C. (2015). Plasma concentration-dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone-21-isonicotinate. Journal of Veterinary Pharmacology and Therapeutics. 38(3), 235-242.
IIEkstrand, C., Ingvast-Larsson, C., Olsén, L., Hedeland, M., Bondesson, U. & Gabrielsson, J. (2016). A quantitative approach to analysing cortisol response in the horse. Journal of Veterinary Pharmacology and Therapeutics. 39(3), 255-263.
IIIEkstrand, C., Bondesson, U., Giving, E., Hedeland, M., Ingvast-Larsson, C., Jacobsen, S., Löfgren, M., Moen, L., Saetra, T. & Ranheim, B. (2017). Disposition and effect of intraarticular administered dexamethasone on lipopolysaccharide-induced inflammation in the equine joint (manuscript).
IVEkstrand, C., Ingvast-Larsson, C., Saetra, T., Giving, E., Moen, L., Rhodin, M. & Ranheim, B. (2017). Intraarticular dexamethasone in an equine model of inflammation: effect on lameness and local joint inflammation (manuscript).
Place of Publication:Uppsala
Publisher:Department of Biomedical Sicences and Veterinary Public Health, Swedish University of Agricultural Sciences
ISBN for printed version:978-91-576-8835-4
ISBN for electronic version:978-91-576-8836-1
ISSN:1652-6880
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Agris subject categories.:L Animal production > L74 Miscellaneous animal disorders
Subjects:(A) Swedish standard research categories 2011 > 3 Medical and Health Sciences > 301 Basic Medicine > Pharmacology and Toxicology
(A) Swedish standard research categories 2011 > 4 Agricultural Sciences > 403 Veterinary Science > Pathobiology
Agrovoc terms:horses, racehorses, inflammation, pharmacokinetics, pharmacodynamics, corticoids, glucocorticoids, dexamethasone, animal diseases, animal welfare, diagnosis, regulations
Keywords:pharmacokinetics, pharmacodynamics, potency, efficacy, turnover model, integrative pharmacology, quantitative pharmacology, corticosteroids, glucocorticoids
URN:NBN:urn:nbn:se:slu:epsilon-e-4020
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-e-4020
ID Code:14190
Faculty:VH - Faculty of Veterinary Medicine and Animal Science
Department:(VH) > Dept. of Biomedical Sciences and Veterinary Public Health
External funders:Stiftelsen Hästforskning
Deposited By: Carl Ekstrand
Deposited On:16 Mar 2017 15:41
Metadata Last Modified:13 Apr 2017 15:15

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