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Plasma concentration-dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone-21-isonicotinate
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry.
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2015 (English)In: Journal of Veterinary Pharmacology and Therapeutics, ISSN 0140-7783, E-ISSN 1365-2885, Vol. 38, no 3, 235-242 p.Article in journal (Refereed) Published
Abstract [en]

Detection times and screening limits (SL) are methods used to ensure that the performance of horses in equestrian sports is not altered by drugs. Drug concentration-response relationship and knowledge of concentration-time profiles in both plasma and urine are required. In this study, dexamethasone plasma and urine concentration-time profiles were investigated. Endogenous hydrocortisone plasma concentrations and their relationship to dexamethasone plasma concentrations were also explored. A single dose of dexamethasone-21-isonicotinate suspension (0.03mg/kg) was administered intramuscularly to six horses. Plasma was analysed for dexamethasone and hydrocortisone and urine for dexamethasone, using UPLC-MS/MS. Dexamethasone was quantifiable in plasma for 8.3 +/- 2.9days (LLOQ: 0.025g/L) and in urine for 9.8 +/- 3.1days (LLOQ: 0.15g/L). Maximum observed dexamethasone concentration in plasma was 0.61 +/- 0.12g/L and in urine 4.2 +/- 0.9g/L. Terminal plasma half-life was 38.7 +/- 19h. Hydrocortisone was significantly suppressed for 140h. The plasma half-life of hydrocortisone was 2.7 +/- 1.3h. Dexamethasone potency, efficacy and sigmoidicity factor for hydrocortisone suppression were 0.06 +/- 0.04g/L, 0.95 +/- 0.04 and 6.2 +/- 4.6, respectively. Hydrocortisone suppression relates to the plasma concentration of dexamethasone. Thus, determination of irrelevant plasma concentrations and SL is possible. Future research will determine whether hydrocortisone suppression can be used as a biomarker of the clinical effect of dexamethasone.

Place, publisher, year, edition, pages
2015. Vol. 38, no 3, 235-242 p.
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Veterinary Science Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-252964DOI: 10.1111/jvp.12175ISI: 000353341300004PubMedID: 25366540OAI: oai:DiVA.org:uu-252964DiVA: diva2:812811
Available from: 2015-05-20 Created: 2015-05-18 Last updated: 2017-12-04Bibliographically approved

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Bondesson, UlfHedeland, Mikael

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