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Drug testing and analysis2023; doi: 10.1002/dta.3543

Ketoprofen in horses: Metabolism, pharmacokinetics, and effects on inflammatory biomarkers.

Abstract: Ketoprofen is an anti-inflammatory drug that is commonly administered to racehorses for the alleviation of musculoskeletal pain and inflammation. This study represents a comprehensive examination of the metabolism (in vivo and in vitro), pharmacokinetics and ex vivo pharmacodynamics, of ketoprofen in horses. The in vitro metabolism as well as specific enzymes responsible for metabolism was determined by incubating liver microsomes and recombinant CYP450 and UGT enzymes with ketoprofen. For the in vivo portion, 15 horses were administered a single intravenous dose of 2.2-mg/kg ketoprofen. Blood and urine samples were collected prior to and up to 120 h post-drug administration. Additional blood samples were collected at select time points and were stimulated with calcium ionophore or lipopolysaccharide, ex vivo, to induce eicosanoid production. Drug, metabolite, and eicosanoid concentrations were determined using LC-MS/MS. Incubation of ketoprofen with equine liver microsomes generated 3-hydroxy ketoprofen, an unidentified hydroxylated metabolite, and ketoprofen glucuronide. Recombinant equine CYP2C23 produced the greatest amount of hydroxylated ketoprofen and recombinant equine UGT1A2 generated ketoprofen glucuronide. Dihydro, 3-hydroxy, and glucuronide metabolites were identified in blood and urine samples. The Vd was 0.280, 0.385, and 0.319 L/kg for total ketoprofen, S (+) ketoprofen, and R (-) ketoprofen, respectively. The mean half-life was 6.01 h for total ketoprofen, 2.22 h for S (+) ketoprofen, and 1.72 h for R (-) ketoprofen. Stimulation of ketoprofen-treated blood with lipopolysaccharide and calcium ionophore resulted in an inhibition of TXB , PGE , PGF , LTB , and 15(s)-HETE production for up to 120 h post-drug administration.
© 2023 John Wiley & Sons Ltd.
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Publication Date: 2023-07-13 PubMed ID: 37439283DOI: 10.1002/dta.3543Google 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.

The research explored the metabolism, pharmacokinetics, and impacts on inflammatory markers of the drug Ketoprofen when used in horses; it demonstrated that the drug inhibits certain eicosanoid production, indicating its anti-inflammatory properties.

Study Overview

To gain a fuller understanding of how Ketoprofen works in horses, this research was broken down into several sections:

  • Observations on how the drug is metabolized both within and outside of the body (in vivo and in vitro)
  • Evaluations of the drug’s pharmacokinetics, which includes its absorption, distribution, metabolism, and excretion
  • Assessments of the drug’s pharmacodynamics, the effects it has and its mechanisms

Metabolism and Enzymes

Researchers began by determining the specific enzymes involved in the metabolism of Ketoprofen by incubating it with horse liver microsomes and two types of enzymes (CYP450 and UGT).

  • They discovered that three byproducts occur when ketoprofen is metabolized: 3-hydroxy ketoprofen, ketoprofen glucuronide, and an unidentified hydroxylated metabolite.
  • The enzymes CYP2C23 and UGT1A2 were found to produce the most hydroxylated ketoprofen and ketoprofen glucuronide respectively.

In Vivo Studies

The researchers then moved on to study how the drug behaves in the horse’s body. They administered a unique 2.2-mg/kg intravenous dose of ketoprofen to 15 horses and tracked its path.

  • The ketoprofen and its metabolites’ concentrations in the blood and urine, collected before and up to 120 hours after administering the drug, provided information about how the drug was processed in the horses’ bodies.
  • The distribution volumes (Vd) and half-lives of ketoprofen and its metabolic versions were determined. The half-life is the time it takes for the drug’s concentration in the body to halve. It was found to be 6.01 hours for total ketoprofen, 2.22 hours for S (+) ketoprofen, and 1.72 hours for R (-) ketoprofen.

Ex Vivo Studies

Lastly, the researchers examined the effects of ketoprofen on eicosanoid production, to understand how it exerts its anti-inflammatory effects.

  • Stimulation of blood (treated with ketoprofen) with lipopolysaccharide and calcium ionophore resulted in an inhibition of specific eicosanoid production (TXB , PGE , PGF , LTB , and 15(s)-HETE), suggesting that ketoprofen could suppress inflammation in this manner.

Cite This Article

APA
Knych HK, McKemie DS, Kass PH, Stanley SD, Blea J. (2023). Ketoprofen in horses: Metabolism, pharmacokinetics, and effects on inflammatory biomarkers. Drug Test Anal. https://doi.org/10.1002/dta.3543

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English

Researcher Affiliations

Knych, Heather K
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
  • Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA.
McKemie, Daniel S
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
Kass, Philip H
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA.
Stanley, Scott D
  • MH Gluck Equine Research Center, University of Kentucky College of Agriculture, Lexington, Kentucky, USA.
Blea, Jeff
  • School of Veterinary Medicine, University of California, Davis, California, USA.

Grant Funding

  • Racing Medication and Testing Consortium
  • California Horse Racing Board

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This article includes 25 references
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Citations

This article has been cited 1 times.
  1. Cysewski P, Jeliński T, Przybyłek M, Mai A, Kułak J. Experimental and Machine-Learning-Assisted Design of Pharmaceutically Acceptable Deep Eutectic Solvents for the Solubility Improvement of Non-Selective COX Inhibitors Ibuprofen and Ketoprofen. Molecules 2024 May 14;29(10).
    doi: 10.3390/molecules29102296pubmed: 38792157google scholar: lookup
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