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Home / Equine Research Bank / J Vet Pharmacol Ther / Meta-Analysis and Mechanism-Based Modeling of Synovial and P...
Journal of veterinary pharmacology and therapeutics2025; doi: 10.1111/jvp.13504

Meta-Analysis and Mechanism-Based Modeling of Synovial and Plasma Pharmacokinetics and Adrenal Suppression Following Intra-Articular Injection of Methylprednisolone Acetate in Horses.

Abstract: This study assesses the pharmacokinetics (PK) of published methylprednisolone (MPL) data in horses following intra-articular (IA) administration of MPL acetate (MPA) and the associated adrenal suppression. The concentrations of MPL/MPA in synovial fluid, blood, and urine, as well as hydrocortisone (HC) in plasma, were digitized from multiple sources in the literature. A minimal physiologically based pharmacokinetic model and a linked indirect response model with a circadian rhythm baseline were applied. Concentrations of MPA in joints followed a triexponential decay, converting to MPL. The clearance of MPL was 797 mL/h/kg via hepatic metabolism (93%) and renal excretion (7%). The persistence of MPL in synovium and plasma for over 500 h was primarily ascribed to slow prodrug dissolution. The formation of MPL from available MPA in SF was rapid. A transit step was needed between the synovium and plasma for MPL absorption. The MPA to MPL bioavailability was dose and/or study dependent; 100% for dosages below 100 mg and 58% for 200 mg. The MPL inhibition of HC production was potent, with an IC of 0.83 ng/mL, and lasted over 50 h. This meta-analysis utilizing a mechanistic modeling approach provided advanced and comprehensive insights on IA MPL PK in horses and was translatable for the PK appreciation of IA MPA dosing in man.
© 2025 John Wiley & Sons Ltd.
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Publication Date: 2025-03-10 PubMed ID: 40059579DOI: 10.1111/jvp.13504Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article performs a meta-analysis and uses a mechanism-based model to evaluate the metabolism and impacts on adrenal function of methylprednisolone acetate when directly injected into a horse’s joints.

Objective of the Study

  • The study is aimed at investigating the pharmacokinetic responses in horses after the intra-articular (directly into a joint) administration of Methylprednisolone Acetate (MPA).
  • The study seeks to understand the pharmacokinetics of methylprednisolone (MPL) by evaluating its concentration in different biological fluids – synovial fluid, blood, and urine, including plasma levels of hydrocortisone (HC).

Methods Used

  • Data were collected from pre-existing literature and used to determine the MPL/MPA and HC concentrations in synovial fluid, plasma, and urine.
  • Researchers applied a minimal physiologically based pharmacokinetic model and an indirect response model with a circadian rhythm baseline to process the data.

Key Findings

  • The study found the concentration of MPA in horse joints followed a tri-exponential decay, slowly converting to MPL.
  • The clearance of MPL was primarily through hepatic metabolism (93%), whereas renal excretion accounted for the remaining 7%.
  • The long-lasting presence of MPL in synovium and plasma (over 500 hours) was primarily ascribed to the slow dissolution of the prodrug.
  • Fast formation of MPL from available MPA in the synovial fluid was observed.
  • A transition step was needed for the absorption of MPL from the synovium to plasma.
  • The dose and/or study dependence of MPA to MPL bioavailability was noted. Bioavailability was 100% for dosages below 100 mg and 58% for a dose of 200 mg.
  • The inhibition of hydrocortisone (HC) production by MPL was quite high (IC of 0.83 ng/mL) and lasted over 50 hours.

Impact of the Study

  • This research provides comprehensive insights into the pharmacokinetics of IA MPL in horses using a mechanistic modeling approach.
  • The findings could be translated to understand the pharmacokinetics of intra-articular MPA dosing in humans, helping in developing better techniques of drug administration in joint therapies.

Cite This Article

APA
Yu R, Jusko WJ. (2025). 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. https://doi.org/10.1111/jvp.13504

Publication

Journal of veterinary pharmacology and therapeutics
ISSN: 1365-2885
NlmUniqueID: 7910920
Country: England
Language: English

Researcher Affiliations

Yu, Ruihong
  • Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, New York, USA.
Jusko, William J
  • Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, New York, USA.

Grant Funding

  • NIGMS NIH HHS

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