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Research article2019Peer reviewed

Plasma Dexamethasone Concentration in Relation to Glucose Response in the Horse

Ekstrand, Carl; Falkeno, Ulrika; Kallings, Peter; Tvedten, Harold; Lilliehook, Inger

Abstract

Therapeutic agents capable of altering the performance of horses are monitored in racing and equestrian sports to guarantee horse welfare, fair competition, and integrity of the sport. Dexamethasone is a common glucocorticoid drug for treating horses. Among other effects, dexamethasone is gluconeogenic and increases blood glucose. In this study, plasma samples from two dexamethasone exposure studies were analyzed for glucose using an automated clinical chemistry analyzer. In study one, dexamethasone-21-isonicotinate was administered to six horses at the dose 30 mu g/kg intramuscularly. In study two, dexamethasone 21-phosphate disodium salt was administered intravenously to six horses as a bolus dose followed by 3 hours of infusion (bolus + infusion) at four different doses (placebo, 0.1 + 0.07 mu g/kg, 1 + 0.7 mu g/kg, and 10 + 7 mu g/kg). Plasma dexamethasone concentrations were linked to plasma glucose concentrations by means of a turnover model. The median (range) pharmacodynamic parameters for glucose response for the two studies were as follows: the EC50 value was 0.84 mu g/L (0.47-1.50) and 0.85 mu g/L (0.75-2.45), the fractional turnover rate of response was 0.18 per h (0.07-0.27) and 0.25 per h (0.17-0.48), and the unaffected baseline of response was 4.20 mmol/L (4.10-6.60) and 5.42 mmol/L (5.22-5.96). These results may be used as input to future studies of the anti- inflammatory response of dexamethasone. The results also enable calculations of irrelevant plasma concentrations to determine whether the presence of a drug is a trace from legitimate medication or not. Therefore, this study provides further evidence for dexamethasone screening limits, which protects the integrity of the sport and the welfare of the horse. (C) 2018 Elsevier Inc. All rights reserved.

Keywords

Glucocorticoids; Anti-doping; Turnover model; Pharmacodynamics; Medication control; Equine

Published in

Journal of Equine Veterinary Science
2019, Volume: 73, pages: 75-80 Publisher: ELSEVIER SCIENCE INC