Meta-Analysis and Physiologically-Based Modeling of the Pharmacokinetics and Pharmacodynamics of Dexamethasone in Horses
Abstract
Purpose 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 50 of 0.038 ng/mL and plasma GLU increases with an EC 50 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.
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BibTeX
@article{yu2026metaanalysis,
title = {{Meta-Analysis and Physiologically-Based Modeling of the Pharmacokinetics and Pharmacodynamics of Dexamethasone in Horses}},
author = {Ruihong Yu and Pierre-Louis Toutain and Carl Ekstrand and William J Jusko},
journal = {Pharmaceutical Research},
year = {2026},
month = jun,
doi = {10.1007/s11095-026-04120-5},
url = {https://hal.science/hal-05797936v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Meta-Analysis and Physiologically-Based Modeling of the Pharmacokinetics and Pharmacodynamics of Dexamethasone in Horses
AU - Ruihong Yu
AU - Pierre-Louis Toutain
AU - Carl Ekstrand
AU - William J Jusko
PY - 2026
DA - 2026/06/19
JO - Pharmaceutical Research
DO - 10.1007/s11095-026-04120-5
UR - https://hal.science/hal-05797936v1
AB - Purpose 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 50 of 0.038 ng/mL and plasma GLU increases with an EC 50 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.
SN - 0724-8741
SN - 1573-904X
ER -