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A quantitative approach to analysing cortisol response in the horse
Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Div Pharmacol & Toxicol, SE-75007 Uppsala, Sweden..
Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Div Pharmacol & Toxicol, SE-75007 Uppsala, Sweden..
Swedish Univ Agr Sci, Dept Biomed Sci & Vet Publ Hlth, Div Pharmacol & Toxicol, SE-75007 Uppsala, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry. Natl Vet Inst SVA, Dept Chem Environm & Feed Hyg, Uppsala, Sweden..
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2016 (English)In: Journal of Veterinary Pharmacology and Therapeutics, ISSN 0140-7783, E-ISSN 1365-2885, Vol. 39, no 3, 255-263 p.Article in journal (Refereed) PublishedText
Abstract [en]

The cortisol response to glucocorticoid intervention has, in spite of several studies in horses, not been fully characterized with regard to the determinants of onset, intensity and duration of response. Therefore, dexamethasone and cortisol response data were collected in a study applying a constant rate infusion regimen of dexamethasone (0.17, 1.7 and 17g/kg) to six Standardbreds. Plasma was analysed for dexamethasone and cortisol concentrations using UHPLC-MS/MS. Dexamethasone displayed linear kinetics within the concentration range studied. A turnover model of oscillatory behaviour accurately mimicked cortisol data. The mean baseline concentration range was 34-57g/L, the fractional turnover rate 0.47-1.5 1/h, the amplitude parameter 6.8-24g/L, the maximum inhibitory capacity 0.77-0.97, the drug potency 6-65ng/L and the sigmoidicity factor 0.7-30. This analysis provided a better understanding of the time course of the cortisol response in horses. This includes baseline variability within and between horses and determinants of the equilibrium concentration-response relationship. The analysis also challenged a protocol for a dexamethasone suppression test design and indicated future improvement to increase the predictability of the test.

Place, publisher, year, edition, pages
2016. Vol. 39, no 3, 255-263 p.
National Category
Pharmacology and Toxicology Veterinary Science
Identifiers
URN: urn:nbn:se:uu:diva-297103DOI: 10.1111/jvp.12276ISI: 000374349500005PubMedID: 26542753OAI: oai:DiVA.org:uu-297103DiVA: diva2:941245
Available from: 2016-06-22 Created: 2016-06-21 Last updated: 2016-06-22Bibliographically approved

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Hedeland, MikaelBondesson, Ulf
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Analytical Pharmaceutical Chemistry
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