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Journal of veterinary pharmacology and therapeutics2013; 37(2); 125-132; doi: 10.1111/jvp.12070

Disposition of methylprednisolone acetate in plasma, urine, and synovial fluid following intra-articular administration to exercised thoroughbred horses.

Abstract: Methylprednisolone acetate (MPA) is commonly administered to performance horses, and therefore, establishing appropriate withdrawal times prior to performance is critical. The objectives of this study were to describe the plasma pharmacokinetics of MPA and time-related urine and synovial fluid concentrations following intra-articular administration to sixteen racing fit adult Thoroughbred horses. Horses received a single intra-articular administration of MPA (100 mg). Blood, urine, and synovial fluid samples were collected prior to and at various times up to 77 days postdrug administration and analyzed using tandem liquid chromatography-mass spectrometry (LC-MS/MS). Maximum measured plasma MPA concentrations were 6.06 ± 1.57 at 0.271 days (6.5 h; range: 5.0-7.92 h) and 6.27 ± 1.29 ng/mL at 0.276 days (6.6 h; range: 4.03-12.0 h) for horses that had synovial fluid collected (group 1) and those that did not (group 2), respectively. The plasma terminal half-life was 1.33 ± 0.80 and 0.843 ± 0.414 days for groups 1 and 2, respectively. MPA was undetectable by day 6.25 ± 2.12 (group 1) and 4.81 ± 2.56 (group 2) in plasma and day 17 (group 1) and 14 (group 2) in urine. MPA concentrations in synovial fluid remained above the limit of detection (LOD) for up to 77 days following intra-articular administration, suggesting that plasma and urine concentrations are not a good indicator of synovial fluid concentrations.
Publication Date: 2013-07-22 PubMed ID: 23876165DOI: 10.1111/jvp.12070Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The study analyzes how the drug Methylprednisolone acetate (MPA) is processed and excreted in the bodies of racing horses after it’s administered into a joint. The results showed that maximum concentrations of the drug in blood occurred within 6.5 to 6.6 hours and became undetectable in blood within 6.25 to 4.81 days and in urine within 17 or 14 days. Despite this, significant levels of the drug could be traced in the synovial fluid of joints for up to 77 days, indicating urine and blood levels may not reliably measure how long the drug remains in a horse’s system after inter-articular administration.

Study Objectives and Methodology

  • The study aimed to track the processing and excretion of Methylprednisolone acetate (MPA) in the bodies of racing horses after intra-articular administration.
  • To do so, the researchers administered the drug to 16 thoroughbred racing horses, then collected and analyzed blood, urine, and synovial fluid samples over a span of 77 days.
  • The liquid chromatography-mass spectrometry (LC-MS/MS) technique was used to analyze these samples.

Results – Plasma Concentrations

  • The highest observed MPA concentrations in blood reached 6.06 ± 1.57 ng/mL at about 6.5 hours post-administration in the first group of horses and 6.27 ± 1.29 ng/mL at about 6.6 hours in the second group.
  • The drug’s half-life in the bloodstream was found to be about 1.33 ± 0.80 days for the first group and 0.843 ± 0.414 days for the second group.
  • By 6.25 ± 2.12 days post-administration in the first group, and 4.81 ± 2.56 days in the second group, MPA became undetectable in blood samples.

Results – Urine Concentrations

  • The drug also became undetectable in urine samples collected by day 17 in the first group and by day 14 in the second group.

Results – Synovial Fluid Concentrations

  • Significantly, the study found that MPA remained within the limit of detection in the horses’ synovial fluid, up to 77 days following intra-articular administration.
  • This suggests that examinations of plasma and urine are not reliable ways to measure the presence and concentrations of MPA in the body after it has been delivered into a joint.

Cite This Article

APA
Knych HK, Harrison LM, Casbeer HC, McKemie DS. (2013). Disposition of methylprednisolone acetate in plasma, urine, and synovial fluid following intra-articular administration to exercised thoroughbred horses. J Vet Pharmacol Ther, 37(2), 125-132. https://doi.org/10.1111/jvp.12070

Publication

ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English
Volume: 37
Issue: 2
Pages: 125-132

Researcher Affiliations

Knych, H K
  • K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA; Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Harrison, L M
    Casbeer, H C
      McKemie, D S

        MeSH Terms

        • Animals
        • Anti-Inflammatory Agents / blood
        • Anti-Inflammatory Agents / pharmacokinetics
        • Anti-Inflammatory Agents / urine
        • Female
        • Horses / blood
        • Horses / urine
        • Injections, Intra-Articular
        • Male
        • Methylprednisolone / analogs & derivatives
        • Methylprednisolone / blood
        • Methylprednisolone / pharmacokinetics
        • Methylprednisolone / urine
        • Methylprednisolone Acetate
        • Physical Conditioning, Animal
        • Synovial Fluid / chemistry

        Citations

        This article has been cited 3 times.
        1. Knych HK, Weiner D, Harrison L, McKemie DS. Pharmacokinetics and pharmacodynamics of intra-articular isoflupredone following administration to horses with lipopolysaccharide-induced synovitis. BMC Vet Res 2022 Dec 13;18(1):436.
          doi: 10.1186/s12917-022-03537-5pubmed: 36514067google scholar: lookup
        2. Ekstrand C, Bondesson U, Giving E, Hedeland M, Ingvast-Larsson C, Jacobsen S, Löfgren M, Moen L, Rhodin M, Saetra T, Ranheim B. Disposition and effect of intra-articularly administered dexamethasone on lipopolysaccharide induced equine synovitis. Acta Vet Scand 2019 Jun 20;61(1):28.
          doi: 10.1186/s13028-019-0464-2pubmed: 31221173google scholar: lookup
        3. Yu R, Jusko WJ. Meta-Analysis and Mechanism-Based Modeling of Synovial and Plasma Pharmacokinetics and Adrenal Suppression Following Intra-Articular Injection of Methylprednisolone Acetate in Horses. J Vet Pharmacol Ther 2025 Jul;48(4):260-273.
          doi: 10.1111/jvp.13504pubmed: 40059579google scholar: lookup