Disposition of isoflupredone acetate in plasma, urine and synovial fluid following intra-articular administration to exercised Thoroughbred horses.
Abstract: The use of isoflupredone acetate in performance horses and the scarcity of published pharmacokinetic data necessitate further study. The objective of the current study was to describe the plasma pharmacokinetics of isoflupredone acetate as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (8 mg) of isoflupredone acetate into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to and at various times up to 28 days post drug administration. All samples were analyzed using liquid chromatography-Mass Spectrometry. Plasma data were analyzed using a population pharmacokinetic compartmental model. Maximum measured plasma isoflupredone concentrations were 1.76 ± 0.526 ng/mL at 4.0 ± 1.31 h and 1.63 ± 0.243 ng/mL at 4.75 ± 0.5 h, respectively, for horses that had synovial fluid collected and for those that did not. The plasma beta half-life was 24.2 h. Isoflupredone concentrations were below the limit of detection in all horses by 48 h and 7 days in plasma and urine, respectively. Isoflupredone was detected in the right antebrachiocarpal and middle carpal joints for 8.38 ± 5.21 and 2.38 ± 0.52 days, respectively. Results of this study provide information that can be used to regulate the use of intra-articular isoflupredone in the horse.
Copyright © 2015 John Wiley & Sons, Ltd.
Publication Date: 2015-09-01 PubMed ID: 26333097DOI: 10.1002/dta.1834Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research study investigates the behavior of the drug isoflupredone acetate inside the bodies of Thoroughbred racing horses after administration. It highlights how long the drug’s presence can be detected in various parts of the horse’s body, such as blood, urine, and synovial fluid.
Objective of the Research
- The main purpose of this study was to detail the pharmacokinetics of isoflupredone acetate in the plasma of horses, as well as gauge the change in concentration of the drug over time in the urine and synovial fluid of horses, following intra-articular administration.
Methodology
- The experiment involved twelve adult Thoroughbred horses fit for racing. These animals were subjected to a single dose (8 mg) of isoflupredone acetate directly into their right antebrachiocarpal joint.
- Blood, urine, and synovial fluid samples were collected from these horses before the drug administration and then periodically over the next 28 days.
- These collected samples were then analyzed using a technique known as liquid chromatography-mass spectrometry.
- The plasma data from all horses were further analyzed using a population pharmacokinetic compartmental model, which helps understand how the drug behaves within an organism.
Results and Observations
- The highest detected plasma isoflupredone concentrations amounted to 1.76 ± 0.526 ng/mL at 4.0 ± 1.31 hours and 1.63 ± 0.243 ng/mL at 4.75 ± 0.5 hours for horses from which synovial fluid was collected, and those from which it was not collected, respectively.
- The half-life of isoflupredone in the horse’s plasma was observed to be about 24.2 hours.
- The drug was no longer present in quantities that could be detected in all horses after 48 hours and 7 days in the plasma and urine, respectively.
- In the right antebrachiocarpal and middle carpal joints, however, isoflupredone could be detected for 8.38 ± 5.21 and 2.38 ± 0.52 days, respectively.
Research Implications
- The findings of this research provide valuable information that could be utilized to make informed assessments about the regulation of intra-articular isoflupredone usage in horses, especially those that participate in racing events. It may assist in better understanding the impact of the drug on a horse’s performance and also help in framing clear policies around drug use in the racing industry.
Cite This Article
APA
Knych HK, Harrison LM, White A, McKemie DS.
(2015).
Disposition of isoflupredone acetate in plasma, urine and synovial fluid following intra-articular administration to exercised Thoroughbred horses.
Drug Test Anal, 8(1), 141-147.
https://doi.org/10.1002/dta.1834 Publication
Researcher Affiliations
- K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, 95616, CA, USA.
- Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, 95616, CA, USA.
- Willow Oak Equine, Woodland, 95695, CA, USA.
- K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, 95616, CA, USA.
- K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, 95616, CA, USA.
MeSH Terms
- Animals
- Chromatography, Liquid / methods
- Female
- Fluprednisolone / analogs & derivatives
- Fluprednisolone / analysis
- Fluprednisolone / blood
- Fluprednisolone / pharmacokinetics
- Fluprednisolone / urine
- Glucocorticoids / analysis
- Glucocorticoids / blood
- Glucocorticoids / pharmacokinetics
- Glucocorticoids / urine
- Horses / blood
- Horses / metabolism
- Horses / urine
- Male
- Substance Abuse Detection / methods
- Synovial Fluid / metabolism
- Tandem Mass Spectrometry / methods
Citations
This article has been cited 2 times.- 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.
- 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.
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