• 1.

    Jeffcott LBRossdale PDFreestone J, et al. An assessment of wastage in Thoroughbred racing from conception to 4 years of age. Equine Vet J 1982; 14:185198.

    • Search Google Scholar
    • Export Citation
  • 2.

    Lidner AVonwittke PDingerkeus A, et al. Causes and rate of training failure in Thoroughbreds. Equine Athlete 1992; 5:17.

  • 3.

    Rossdale PDHopes RDigby NJ, et al. Epidemiological study of wastage among racehorses 1982 and 1983. Vet Rec 1985; 116:6669.

  • 4.

    United States Equestrian Federation. 2012 guidelines for drugs and medications. Available at: www.usef.org/issuu/flipbook.ashx?docname=drugsmedsguidelines2012&pdfurl=http://www.usef.org/documents/drugsMeds/DrugsMedsGuidelines2012.pdf. Accessed Apr 25, 2012.

    • Search Google Scholar
    • Export Citation
  • 4.

    Federation Equestre Internationale. Current regulations on doping and controlled medication. FEI list of detection times. Available at: www.usef.org/issuu/flipbook.ashx?docname=drugsmedsguidelines2012&pdfurl=http://www.usef.org/documents/drugsMeds/DrugsMedsGuidelines2012.pdf. Accessed Apr 25, 2012.

    • Search Google Scholar
    • Export Citation
  • 5.

    Dulin JADrost WTPhelps MA, et al. Influence of exercise on the distribution of technetium Tc 99m medronate following intra-articular injection in horses. Am J Vet Res 2012; 73:418425.

    • Search Google Scholar
    • Export Citation
  • 6.

    Ferguson DHoenig M. Corticosteroids, mineral corticosteroids, and steroid synthesis inhibitors. In: Veterinary pharmacology therapeutics. 8th ed. Ames, Iowa: Iowa State University Press, 2001:649671.

    • Search Google Scholar
    • Export Citation
  • 7.

    Bottoms GDRoesel OFRausch FD, et al. Circadian variation in plasma cortisol and corticosterone in pigs and mares. Am J Vet Res 1972; 33:785790.

    • Search Google Scholar
    • Export Citation
  • 8.

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

    • Search Google Scholar
    • Export Citation
  • 9.

    Larsson MEkman LPersson S. Plasma cortisol in the horse, diurnal rhythm and effects of exogenous ACTH. Acta Vet Scand 1979; 20:1624.

    • Search Google Scholar
    • Export Citation
  • 10.

    Toutain PLOukessou MAutefage A, et al. Diurnal and episodic variations of plasma hydrocortisone concentrations in horses. Domest Anim Endocrinol 1988; 5:5559.

    • Search Google Scholar
    • Export Citation
  • 11.

    Zolovick AEleftheriou BE. Diurnal variation in plasma glucocorticosteroid levels in the horse. J Endocrinol 1966; 35:249253.

  • 12.

    Gordon MEBetros CLManso HC. Exercise-induced alterations in plasma concentrations of ghrelin, adiponectin, leptin, glucose, insulin, and cortisol in horses. Vet J 2007; 173:532540.

    • Search Google Scholar
    • Export Citation
  • 13.

    Toutain PLLaurentie MAutefage A, et al. Hydrocortisone secretion: production rate and pulse characterization by numerical deconvolution. Am J Physiol 1988; 255:E688E659.

    • Search Google Scholar
    • Export Citation
  • 14.

    Autefage AAlvinerie MToutain PL. Synovial fluid and plasma kinetics of methylprednisolone acetate in horses following intra-articular administration of methylprednisolone acetate. Equine Vet J 1986; 18:193198.

    • Search Google Scholar
    • Export Citation
  • 15.

    Boumpas DTChrousos GPWilder RL, et al. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med 1993; 119:11981208.

    • Search Google Scholar
    • Export Citation
  • 16.

    Alex PArthur E. Influence of intraarticular corticosteroid administration on serum cytokines in rheumatoid arthritis. Clin Rheumatol 2007; 26:845848.

    • Search Google Scholar
    • Export Citation
  • 17.

    Soma LRUboh CELuo Y, et al. Pharmacokinetics of methylprednisolone acetate after intra-articular administration and its effect on endogenous hydrocortisone and cortisone secretion in horses. Am J Vet Res 2006; 67:654662.

    • Search Google Scholar
    • Export Citation
  • 18.

    Armstrong RDEnglish JGibson T, et al. Serum methylprednisolone levels following intra-articular injection of methylprednisolone acetate. Ann Rheum Dis 1981; 40:571574.

    • Search Google Scholar
    • Export Citation
  • 19.

    Lillich JDBertone ALSchmall LM, et al. Plasma, urine, and synovial fluid disposition of methylprednisolone acetate and isoflupredone acetate after intra-articular administration in horses. Am J Vet Res 1996; 57:187192.

    • Search Google Scholar
    • Export Citation
  • 20.

    Ferris DJFrisbie DDMcIlwraith CW, et al. Current joint therapy usage in equine practice: a survey of veterinarians 2009. Equine Vet J 2011; 43:530535.

    • Search Google Scholar
    • Export Citation
  • 21.

    Kronenberg H. Williams textbook of endocrinology. 11th ed. Philadelphia: Saunders Elsevier, 2008:445494.

  • 22.

    Panusa A. A rapid and sensitive LC-ESI-MS/MS method for detection and quantitation of methylprednisolone and methylprednisolone acetate in rat plasma after intra-articular administration. J Pharm Biomed Anal 2010; 51:691697.

    • Search Google Scholar
    • Export Citation

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Pharmacokinetics of methylprednisolone acetate after intra-articular administration and subsequent suppression of endogenous hydrocortisone secretion in exercising horses

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  • 1 Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.
  • | 2 Department of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH 43210.
  • | 3 Department of Orthopedics, College of Medicine, The Ohio State University, Columbus, OH 43210.
  • | 4 Comparative Orthopaedic Research Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210.

Abstract

Objective—To determine the pharmacokinetics of methylprednisolone (MP) and the relationship between MP and hydrocortisone (HYD) concentrations in plasma and urine after intra-articular (IA) administration of 100 or 200 mg of MP acetate (MPA) to horses.

Animals—Five 3-year-old Thoroughbred mares.

Procedures—Horses exercised on a treadmill 3 times/wk during the study. Horses received 100 mg of MPA IA, then 8 weeks later received 200 mg of MPA IA. Plasma and urine samples were obtained at various times for 8 weeks after horses received each dose of MPA; concentrations of MP and HYD were determined. Pharmacokinetic-pharmacodynamic estimates for noncompartmental and compartmental parameters were determined.

Results—Maximum concentration of MP in plasma was similar for each MPA dose; concentrations remained greater than the lower limit of quantitation for 18 and 7 days after IA administration of 200 and 100 mg of MPA, respectively. Maximum concentration and area under the observed concentration-time curve for MP in urine were significantly higher (approximately 10-and 17-fold, respectively) after administration of 200 versus 100 mg of MPA. Hydrocortisone concentration was below quantifiable limits for ≥ 48 hours in plasma and urine of all horses after administration of each MPA dose.

Conclusions and Clinical Relevance—Pharmacokinetics of MP may differ among IA MPA dosing protocols, and MP may be detected in plasma and urine for a longer time than previously reported. This information may aid veterinarians treating sport horses. Further research is warranted to determine whether plasma HYD concentration can aid identification of horses that received exogenous glucocorticoids.

Contributor Notes

Supported by Pfizer Inc and the United States Equestrian Federation.

The authors thank Drs. Akikazu Ishihara, Stephen Schumacher, Thomas Lomangino, Jennifer Dulin, Emily Falk, Carissa Norquest, and Brian Johnson for technical assistance; Dr. Steven Kamerling for assistance with data analysis; and Tim Vojt for assistance with preparation of illustrations.

Address correspondence to Dr. Bertone (bertone.1@osu.edu).