• 1.

    Peroni DL, Stanley S, Kollias-Baker C, et alPrednisone per os is likely to have limited efficacy in horses. Equine Vet J 2002;34:283287.

    • Search Google Scholar
    • Export Citation
  • 2.

    Buechner-Maxwell V. Anti-inflammatory actions of glucocorticoids: molecular mechanisms and the RAO horse, in Proceedings. Am Coll Vet Intern Med 2004;151153.

    • Search Google Scholar
    • Export Citation
  • 3.

    Irvine CH, Alexander SL. Factors affecting the circadian rhythm in plasma cortisol concentrations in the horse. Domest Anim Endocrinol 1994;11:227238.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Barnes PJ. Anti-inflammatory actions of glucocorticoids: molecular mechanisms. Clin Sci 1998;94:557572.

  • 5.

    Johnson PJ, Slight SH, Venkataseshu GK, et alGlucocorticoids and laminitis in the horse. Vet Clin North Am Equine Pract 2002;18:219236.

  • 6.

    Stahn C, Löwenberg M, Hommes DW, et alMolecular mechanisms of glucocorticoid action and selective glucocorticoid receptor agonists. Mol Cell Endocrinol 2007;275:7178.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Clark AR. Anti-inflammatory functions of glucocorticoid-induced genes. Mol Cell Endocrinol 2007;275:7997.

  • 8.

    Song IH, Buttgereit F. Non-genomic glucocorticoid effects to provide the basis for new drug developments. Mol Cell Endocrinol 2006;246:142146.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Guyton AC, Hall JE. Adrenocortical hormones. In: Guyton AC, Hall JE, eds. Textbook of medical physiology. 11th ed. Philadelphia: Elsevier, 2006;945956.

    • Search Google Scholar
    • Export Citation
  • 10.

    Tiley HA, Geor RJ, McCutcheon LJ. Effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. Am J Vet Res 2007;68:753759.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    MacHarg MA, Bottoms GD, Carter GK, et alEffects of multiple intramuscular injections and doses of dexamethasone on plasma cortisol concentrations and adrenal responses to ACTH in horses. Am J Vet Res 1985;46:22852287.

    • Search Google Scholar
    • Export Citation
  • 12.

    Rush BR, Trevino IC, Matson CJ, et alSerum cortisol concentrations in response to incremental doses of inhaled beclomethasone diproprionate. Equine Vet J 1999;31:258261.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Picandet V, Leguillette R, Lavoie JP. Comparison of efficacy and tolerability of isoflupredone and dexamethasone in the treatment of horses affected with recurrent airway obstruction (‘heaves'). Equine Vet J 2003;35:419424.

    • Search Google Scholar
    • Export Citation
  • 14.

    Toutain PL, Brandon RA, de Pomyers H, et alDexamethasone and prednisolone in the horse: pharmacokinetics and action on the adrenal gland. Am J Vet Res 1984;45:17501756.

    • Search Google Scholar
    • Export Citation
  • 15.

    Soma LR, Uboh CE, Lou Y, et alPharmacokinetics of dexamethasone with pharmacokinetic/pharmacodynamic model of the effect of dexamethasone on endogenous hydrocortisone and cortisone in the horse. J Vet Pharmacol Ther 2005;28:7180.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Slone DE, Purohit RC, Ganjam VK, et alSodium retention and cortisol (hydrocortisone) suppression caused by dexamethasone and triamcinolone in equids. Am J Vet Res 1983;44:280283.

    • Search Google Scholar
    • Export Citation
  • 17.

    Rush BR, Worster AA, Flamino MJ, et alAlteration in adrenocortical function in horses with recurrent airway obstruction after aerosol and parenteral administration of beclomethasone diproprionate and dexamethasone, respectively. Am J Vet Res 1998;59:10441047.

    • Search Google Scholar
    • Export Citation
  • 18.

    Chen CL, Sailor JA, Collier J, et alSynovial and serum levels of triamcinolone following intra-articular administration of triamcinolone in the horse. J Vet Pharmacol Ther 1992;15:240246.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Lapointe JM, Lavoie JP, Vrins AA. Effects of triamcinolone acetonide on pulmonary function and bronchoalveolar lavage cytologic features in horses with chronic obstructive pulmonary disease. Am J Vet Res 1993;54:13101316.

    • Search Google Scholar
    • Export Citation
  • 20.

    Cunningham FE, Rogers S, Fischer JH, et alThe pharmacokinetics of dexamethasone in the Thoroughbred racehorse. J Vet Pharmacol Ther 1996;19:6871.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Robinson NE, Peroni D, Stanley S, et alWhy is oral prednisone ineffective for treatment of heaves?, in Proceedings. 46th Annu Conv Am Assoc Equine Pract 2000;266267.

    • Search Google Scholar
    • Export Citation
  • 22.

    Traub-Dargatz JL, McKinnon AO, Thrall MA, et alEvaluation of clinical signs of disease, bronchoalveolar and tracheal wash analysis, and arterial blood gas tensions in 13 horses with chronic obstructive pulmonary disease treated with prednisone, methyl sulfonmethane, and clenbuterol hydrochloride. Am J Vet Res 1992;53:19081916.

    • Search Google Scholar
    • Export Citation
  • 23.

    Robinson NE, Jackson C, Jefcoat A, et alEfficacy of three corticosteroids for the treatment of heaves. Equine Vet J 2002;34:1722.

  • 24.

    Cornelisse CJ, Robinson NE, Berney CE, et alEfficacy of oral and intravenous dexamethasone in horses with recurrent airway obstruction. Equine Vet J 2004;36:426430.

    • Search Google Scholar
    • Export Citation
  • 25.

    DeLuca L, Erb HN, Young JC, et alThe effect of adding oral dexamethasone to feed alterations on the airway cell inflammatory gene expression in stabled horses affected with recurrent airway obstruction. J Vet Intern Med 2008;22:427435.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    Cherlet M, Baere S, DeBacker P. Quantitative determination of dexamethasone in bovine milk by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2004;805:5765.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Zolovick A, Upson DW, Eleftheriou BE. Diurnal variation in plasma glucocorticosteroid levels in the horse (Equus caballus). J Endocrinol 1966;35:249253.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Bottoms GD, Roesel OF, Rausch FD, et alCircadian variation in plasma cortisol and corticosterone in pigs and mares. Am J Vet Res 1972;33:785790.

    • Search Google Scholar
    • Export Citation
  • 29.

    Hoffsis GF, Murdick PW, Tharp VL, et alPlasma concentrations of cortisol and corticosterone in the normal horse. Am J Vet Res 1970;31:13791387.

    • Search Google Scholar
    • Export Citation
  • 30.

    Toutain PL, Oukessou M, Autefage A, et alDiurnal and episodic variations of plasma hydrocortisone concentrations in horses. Domest Anim Endocrinol 1988;5:5559.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Hoffsis GF, Murdick PW. The plasma concentrations of corticosteroids in normal and diseased horses. J Am Vet Med Assoc 1970;157:15901594.

    • Search Google Scholar
    • Export Citation
  • 32.

    Boothe DM. Veterinary compounding in small animals: a clinical pharmacologist's perspective. Vet Clin North Am Small Anim Pract 2006;36:11291173.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Osborne MO. Compounding issues resurface in wake of ponies' death. Incorrrect dosage of selenium in compounded medicine proved fatal. J Am Vet Med Assoc 2009;234:1514.

    • Search Google Scholar
    • Export Citation
  • 34.

    Melby JC. Clinical pharmacology of systemic corticosteroids. Annu Rev Pharmacol Toxicol 1977;17:511527.

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Pharmacokinetics and pharmacodynamics of dexamethasone after oral administration in apparently healthy horses

Jason A. GradyVeterinary Medical Teaching Hospital, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Elizabeth G. DavisVeterinary Medical Teaching Hospital, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Butch KuKanichDepartment of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Amanda B. SherckVeterinary Medical Teaching Hospital, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Abstract

Objective—To assess pharmacokinetic and pharmacodynamic properties of dexamethasone administered PO as a solution or powder, compared with properties of dexamethasone solution administered IV, in apparently healthy horses.

Animals—6 adult horses.

Procedures—Serum cortisol concentration for each horse was determined before each treatment (baseline values). Dexamethasone (0.05 mg/kg) was administered PO (in solution or powdered form) or IV (solution) to horses from which feed had or had not been withheld (unfed and fed horses, respectively). Each horse received all 6 treatments in random order at 2-week intervals; PO and IV administrations of dexamethasone were accompanied by IV or PO sham treatments, respectively. Plasma dexamethasone and serum cortisol concentrations were assessed at predetermined intervals.

Results—Maximum plasma dexamethasone concentration after PO administration of powdered dexamethasone in unfed horses was significantly higher than the maximum plasma concentration after PO administration of dexamethasone solution in unfed or fed horses. Mean bioavailability of dexamethasone ranged from 28% to 66% but was not significantly different among horses receiving either formulation PO in the unfed or fed state. After dexamethasone treatment PO or IV, serum cortisol concentrations were significantly less than baseline at 1 to 72 hours in unfed horses and at 2 to 48 hours in fed horses.

Conclusions and Clinical Relevance—PO or IV administration of dexamethasone resulted in suppression of cortisol secretion in unfed and fed adult horses; the magnitude of suppression did not differ among treatment groups, and serum cortisol concentrations returned to baseline after 48 to 72 hours.

Abstract

Objective—To assess pharmacokinetic and pharmacodynamic properties of dexamethasone administered PO as a solution or powder, compared with properties of dexamethasone solution administered IV, in apparently healthy horses.

Animals—6 adult horses.

Procedures—Serum cortisol concentration for each horse was determined before each treatment (baseline values). Dexamethasone (0.05 mg/kg) was administered PO (in solution or powdered form) or IV (solution) to horses from which feed had or had not been withheld (unfed and fed horses, respectively). Each horse received all 6 treatments in random order at 2-week intervals; PO and IV administrations of dexamethasone were accompanied by IV or PO sham treatments, respectively. Plasma dexamethasone and serum cortisol concentrations were assessed at predetermined intervals.

Results—Maximum plasma dexamethasone concentration after PO administration of powdered dexamethasone in unfed horses was significantly higher than the maximum plasma concentration after PO administration of dexamethasone solution in unfed or fed horses. Mean bioavailability of dexamethasone ranged from 28% to 66% but was not significantly different among horses receiving either formulation PO in the unfed or fed state. After dexamethasone treatment PO or IV, serum cortisol concentrations were significantly less than baseline at 1 to 72 hours in unfed horses and at 2 to 48 hours in fed horses.

Conclusions and Clinical Relevance—PO or IV administration of dexamethasone resulted in suppression of cortisol secretion in unfed and fed adult horses; the magnitude of suppression did not differ among treatment groups, and serum cortisol concentrations returned to baseline after 48 to 72 hours.

Contributor Notes

Supported by the Kansas State University Mentored Clinical, Applied or Translational Research Grant and the Kansas Horse Racing Commission.

Presented in abstract form at the American College of Veterinary Internal Medicine Conference, Seattle, June 2007.

Dr. Grady's present address is Sapulpa Equine Hospital, 12226 Heywood Hill Rd, Sapulpa, OK 74066.

Address correspondence to Dr. Grady (dr.grady@sapulpaequine.com).