title: A quantitative approach to analysing cortisol response in the horse.
abstract: 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 17 μg/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 34-57 μg/L, the fractional turnover rate 0.47-1.5 1/h, the amplitude parameter 6.8-24 μg/L, the maximum inhibitory capacity 0.77-0.97, the drug potency 6-65 ng/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.
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Ekstrand
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Ingvast-Larsson
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Olsén
authors.affiliation: Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA), Uppsala, Sweden.|Department of Medicinal Chemistry, Division of Analytical Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Hedeland
authors.affiliation: Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute (SVA), Uppsala, Sweden.|Department of Medicinal Chemistry, Division of Analytical Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: U
authors.initials: U
authors.lastname: Bondesson
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Gabrielsson
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006736:Horses / Q000097:blood*; D006854:Hydrocortisone / Q000097:blood*; D008297:Male
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D006854:Hydrocortisone