Serum concentrations, pharmacokinetic/pharmacodynamic modeling, and effects of dexamethasone on inflammatory mediators following intravenous and oral administration to exercised horses.
Administration, Intravenous
Administration, Oral
Animals
Anti-Inflammatory Agents
/ administration & dosage
Chromatography, Liquid
/ methods
Dexamethasone
/ administration & dosage
Glucocorticoids
/ administration & dosage
Half-Life
Horses
Inflammation
/ drug therapy
Inflammation Mediators
/ metabolism
Inhibitory Concentration 50
Models, Biological
Tandem Mass Spectrometry
/ methods
Time Factors
Tissue Distribution
corticosteroid
cortisol
dexamethasone
horse
inflammation
Journal
Drug testing and analysis
ISSN: 1942-7611
Titre abrégé: Drug Test Anal
Pays: England
ID NLM: 101483449
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
11
03
2020
revised:
13
05
2020
accepted:
17
05
2020
pubmed:
22
5
2020
medline:
29
6
2021
entrez:
22
5
2020
Statut:
ppublish
Résumé
Corticosteroids are potent anti-inflammatory drugs and as such are commonly administered to performance and racehorses. The objectives of the current study were to describe blood and urine concentrations and the pharmacokinetics and effects on cortisol and inflammatory mediator concentrations, following intravenous and oral administration to 12 exercised horses. Horses received an intravenous administration of 40 mg of dexamethasone sodium phosphate and 20 mg of dexamethasone tablets with a 4 week washout in between administrations. Blood and urine samples were collected prior to and for up to 96 hours post drug administration. Whole blood samples were collected at various time points and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. The concentrations of dexamethasone and eicosanoids were measured using LC-MS/MS and the concentrations from both routes of administration fit simultaneously using a three-compartment pharmacokinetic model. A turnover model with inhibition of K
Substances chimiques
Anti-Inflammatory Agents
0
Glucocorticoids
0
Inflammation Mediators
0
dexamethasone 21-phosphate
2BP70L44PR
Dexamethasone
7S5I7G3JQL
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1087-1101Subventions
Organisme : California Horse Racing Board and the California Department of Food and Agriculture's Equine Medication Monitoring Program
Informations de copyright
© 2020 John Wiley & Sons, Ltd.
Références
ARCI. Available at: https://www.arci.com/wp-content/uploads/2019/12/2019_12_CTS_V4_2.pdf%0A, n.d.
EHSLC. Available at: https://www.ehslc.com/detection-times, n.d.
USEF Medication Guidelines. Available at: https://www.usef.org/compete/resources-forms/rules-regulations/drugs-medications, n.d.
Gryglewski RJ. Steroid hormones, anti-inflammatory steroids and prostaglandins. Pharmacol Res Commun. 1976;8(4):337-348.
Blackwell GJ, Carnuccio R, Di Rosa M, Flower RJ, Parente L, Persico P. Macrocortin: a polypeptide causing the anti-phospholipase effect of glucocorticoids. Nature. 1980;287(5778):147-149.
Granström E. The arachidonic acid cascade. The prostaglandins, thromboxanes and leukotrienes. Inflammation. 1984;8 Suppl:S15-S25.
Soma LR, Uboh CE, Liu Y, et al. Pharmacokinetics of dexamethasone following intra-articular, intravenous, intramuscular, and oral administration in horses and its effects on endogenous hydrocortisone. J Vet Pharmacol Ther. 2013;36(2):181-191.
Soma LR, Uboh CE, Luo Y, Guan F, Moate PJ, Boston RC. Pharmacokinetics of dexamethasone with pharmacokinetic/pharmacodynamic model of the effect of dexamethasone on endogenous hydrocortisone and cortisone in the horse. J Vet Pharmacol Ther. 2005;28(1):71-80.
Grady JA, Davis EG, KuKanich B, Sherck AB. Pharmacokinetics and pharmacodynamics of dexamethasone after oral administration in apparently healthy horses. Am J Vet Res. 2010;71(7):831-839.
Toutain PL, Brandon RA, de Pomyers H, Alvinerie M, Baggot JD. Dexamethasone and prednisolone in the horse: pharmacokinetics and action on the adrenal gland. Am J Vet Res. 1984;45:1750-1756.
Ekstrand C, Ingvast-Larsson C, Olsén L, Hedeland M, Bondesson U, Gabrielsson J. A quantitative approach to analysing cortisol response in the horse. J Vet Pharmacol Ther. 2016;39(3):255-263.
Ekstrand C, Bondesson U, Gabrielsson J, et al. Plasma concentration-dependent suppression of endogenous hydrocortisone in the horse after intramuscular administration of dexamethasone-21-isonicotinate. J Vet Pharmacol Ther. 2015;38(3):235-242.
Mangal D, Uboh CE, Soma LR. Analysis of bioactive eicosanoids in equine plasma by stable isotope dilution reversed-phase liquid chromatography/multiple reaction monitoring mass spectrometry. Rapid Commun Mass Spectrom. 2011;25(5):585-598.
Knych HK, Arthur RM, McKemie DS, Baden R, Oldberg N, Kass PH. Pharmacokinetics of intravenous flumetasone and effects on plasma hydrocortisone concentrations and inflammatory mediators in the horse. Equine Vet J. 2019;51(2):238-245.
Mangal D, Uboh CE, Soma LR, Liu Y. Inhibitory effect of triamcinolone acetonide on synthesis of inflammatory mediators in the equine. Eur J Pharmacol. 2014;736:1-9.
Knych HK, Arthur RM, Mitchell MM, et al. Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses. Drug Test Anal. 2015;7(7):619-625. https://doi.org/10.1002/dta.1737
FDA, CDER. Bioanalytical Method Validation Guidance for Industry Biopharmaceutics Contains Nonbinding Recommendations, 2018.
Fu JY, Masferrer JL, Seibert K, Raz A, Needleman P. The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. J Biol Chem. 1990;265:16737-16740.
Hempel SL, Monick MM, Hunninghake GW. Lipopolysaccharide induces prostaglandin H synthase-2 protein and mRNA in human alveolar macrophages and blood monocytes. J Clin Invest. 1994;93(1):391-396.
The role of lipocortin-1 in dexamethasone-induced suppression of PGE2 and TNF alpha release from human peripheral blood mononuclear cells. British Journal of Pharmacology. 1996;117(7):1449-1456.
Tuure L, Hämäläinen M, Whittle BJ, Moilanen E. Microsomal prostaglandin E synthase-1 expression in inflammatory conditions is downregulated by dexamethasone: seminal role of the regulatory phosphatase MKP-1. Front Pharmacol. 2017;8:646-657.
Riddick CA, Ring WL, Baker JR, Hodulik CR, Bigby TD. Dexamethasone increases expression of 5-lipoxygenase and its activating protein in human monocytes and THP-1 cells. Eur J Biochem. 1997;246(1):112-118.
Lee SJ, Seo KW, Kim CD. LPS increases 5-LO expression on monocytes via an activation of Akt-Sp1/NF-κB pathways. Korean J Physiol Pharmacol. 2015;19(3):263-268.
Almawi W, Melemedjian O. Negative regulation of nuclear factor-kappaB activation and function by glucocorticoids. J Mol Endocrinol. 2002;28(2):69-78.
De Bosscher K, Vanden Berghe W, Haegeman G. Mechanisms of anti-inflammatory action and of immunosuppression by glucocorticoids: negative interference of activated glucocorticoid receptor with transcription factors. J Neuroimmunol. 2000;109(1):16-22.
Samuelsson B, Dahlen S, Lindgren J, Rouzer C, Serhan C. Leukotrienes and lipoxins: structures, biosynthesis, and biological effects. Science. 1987;237:1171-1176.
Ford-Hutchinson AW. Arachidonate 15-lipoxygenase; characteristics and potential biological significance. Eicosanoids. 1991;4(2):65-74.
Badr KF. 15-Lipoxygenase products as leukotriene antagonists: therapeutic potential in glomerulonephritis. Kidney Int Suppl. 1992;38:S101-S108.
Serhan CN. Lipoxin biosynthesis and its impact in inflammatory and vascular events. Biochim Biophys Acta. 1994;1212(1):1-25.
Tejera N, Boeglin WE, Suzuki T, Schneider C. COX-2-dependent and -independent biosynthesis of dihydroxy-arachidonic acids in activated human leukocytes. J Lipid Res. 2012;53(1):87-94.