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Pharmaceutical research2026; doi: 10.1007/s11095-026-04120-5

Meta-Analysis and Physiologically-Based Modeling of the Pharmacokinetics and Pharmacodynamics of Dexamethasone in Horses.

Abstract: Dexamethasone (DEX) is widely used in equine practice for its potent anti-inflammatory effects and diverse studies have examined its pharmacology in horses. We integrated all available pharmacokinetic (PK) and pharmacodynamic (PD) data from 12 studies to quantify DEX disposition and endocrine effects in horses. Methods: DEX concentrations in blood, urine and synovial fluid, plus cortisol (CTS) and glucose (GLU) in plasma, following various administration routes (intravenous (IV), intramuscular (IM), intra-articular, oral) were available from original studies or digitized from literature. A minimal physiologically-based PK model and linked indirect response PD models were applied. Results: The mean clearance of DEX was 344 mL/h/kg via hepatic metabolism (98%) and renal excretion (2%). Due to nonlinear tissue binding, DEX generally exhibited a prolonged terminal phase in plasma, maintaining concentrations above a designated plasma threshold of 5 pg/mL for 67 h following 0.05 mg/kg IV dose. Dosing input parameters of DEX varied markedly across dosing routes and prodrug formulations (alcohol, isonicotinate, phosphate), with bioavailability ranging 37 ~ 100%. Oral and pro-drug doses produced rapid absorption, except for IM DEX-isonicotinate that exhibited slow (flip-flop) availability. Adrenal suppression with an IC of 0.038 ng/mL and plasma GLU increases with an EC of 0.79 ng/mL were observed that commonly persisted for 2 ~ 4 days after single dose. Conclusions: This meta-analysis utilized a mechanistic and physiologically-based modeling framework to provide global perspectives that may promote the rational use of DEX in equine medicine and support evidence-based regulatory decisions.
© 2026. The Author(s).
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Publication Date: 2026-06-19 PubMed ID: 42321583PubMed Central: 6185996DOI: 10.1007/s11095-026-04120-5Google Scholar: Lookup
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  • Journal Article

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.

Overview

  • This study combined data from multiple sources to analyze how dexamethasone (DEX), a potent anti-inflammatory drug, is processed in horses and how it affects their endocrine system.
  • The goal was to model the drug’s behavior in the body (pharmacokinetics) and its biological effects (pharmacodynamics) to better guide usage in veterinary practice.

Study Background and Purpose

  • Dexamethasone is commonly used in horses to reduce inflammation, but there is variability in the drug’s behavior depending on the administration route and formulation.
  • Past studies have investigated DEX pharmacology separately; this work integrated data from 12 studies to create a comprehensive and mechanistic understanding.
  • The study focused on blood, urine, and synovial fluid concentrations of DEX, and also measured related endocrine markers like cortisol and glucose in plasma.

Data Collection and Methods

  • Data was gathered from various administration routes: intravenous (IV), intramuscular (IM), intra-articular (joint injection), and oral.
  • Measured parameters included DEX concentrations and hormone markers such as cortisol (CTS) and glucose (GLU) after dosing.
  • A physiologically-based pharmacokinetic (PBPK) model was used, which incorporates biological processes and organ functions to describe drug absorption, distribution, metabolism, and excretion.
  • In addition, indirect response pharmacodynamic (PD) models linked drug concentration to biological effects like adrenal suppression and changes in plasma glucose.

Key Pharmacokinetic Findings

  • The average clearance (removal rate) of DEX from horse bodies was 344 mL/h/kg, primarily through hepatic metabolism (98%) and minimally via renal excretion (2%).
  • DEX displayed nonlinear tissue binding, meaning the drug’s interaction with body tissues changes with concentration, leading to a prolonged terminal elimination phase in plasma.
  • After a 0.05 mg/kg IV dose, plasma DEX levels remained above 5 pg/mL for about 67 hours, indicating a long-lasting presence in the bloodstream.
  • The bioavailability (the fraction of drug reaching systemic circulation) varied widely (37% to 100%) depending on administration routes and prodrug formulations (such as alcohol, isonicotinate, phosphate derivatives).
  • Most oral and prodrug forms showed rapid absorption; however, IM DEX-isonicotinate exhibited slow (flip-flop) kinetics where absorption was the rate-limiting step, leading to delayed availability.

Pharmacodynamic Effects

  • Adrenal suppression was observed, quantified by an inhibitory concentration (IC) of 0.038 ng/mL, indicating the concentration of DEX causing suppression of cortisol production.
  • Plasma glucose levels increased as a response to DEX, with an effective concentration (EC) of 0.79 ng/mL, suggesting metabolic effects on glucose regulation.
  • These endocrine effects typically persisted for 2 to 4 days following a single dose, reflecting the prolonged duration of drug action.

Conclusions and Implications

  • The integrated meta-analysis provided a global, mechanistic framework to understand DEX pharmacokinetics and pharmacodynamics in horses.
  • The PBPK and PD models allow prediction of drug behavior and effects across different dosing strategies and formulations.
  • This approach supports more rational, evidence-based use of dexamethasone in equine medicine by helping veterinarians tailor dosing.
  • Results can also inform regulatory decisions regarding dosing limits and withdrawal times to ensure safety and efficacy.

Cite This Article

APA
Yu R, Toutain PL, Ekstrand C, Jusko WJ. (2026). Meta-Analysis and Physiologically-Based Modeling of the Pharmacokinetics and Pharmacodynamics of Dexamethasone in Horses. Pharm Res. https://doi.org/10.1007/s11095-026-04120-5

Publication

Pharmaceutical research
ISSN: 1573-904X
NlmUniqueID: 8406521
Country: United States
Language: English

Researcher Affiliations

Yu, Ruihong
  • Division of Pharmacokinetics, Pharmacodynamics, and Systems Pharmacology, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA, 404 Pharmacy Building, 14214-8033.
Toutain, Pierre-Louis
  • Department of Comparative Biomedical Sciences, The Royal Veterinary College, University of London, London, UK.
Ekstrand, Carl
  • Department of Animal Biosciences, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Jusko, William J
  • Division of Pharmacokinetics, Pharmacodynamics, and Systems Pharmacology, Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA, 404 Pharmacy Building, 14214-8033. wjjusko@buffalo.edu.

Grant Funding

  • R35-GM131800 / NIGMS NIH HHS
  • 82204508 / National Natural Science Foundation of China

Conflict of Interest Statement

Declarations. Ethics Statement: The authors have nothing to declare. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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