Pharmacokinetics and effects on thromboxane B2 production following intravenous administration of flunixin meglumine to exercised thoroughbred horses.
Abstract: Flunixin meglumine is commonly used in horses for the treatment of musculoskeletal injuries. The current ARCI threshold recommendation is 20 ng/mL when administered at least 24 h prior to race time. In light of samples exceeding the regulatory threshold at 24 h postadministration, the primary goal of the study reported here was to update the pharmacokinetics of flunixin following intravenous administration, utilizing a highly sensitive liquid chromatography-mass spectrometry (LC-MS). An additional objective was to characterize the effects of flunixin on COX-1 and COX-2 inhibition when drug concentrations reached the recommended regulatory threshold. Sixteen exercised adult horses received a single intravenous dose of 1.1 mg/kg. Blood samples were collected up to 72 h postadministration and analyzed using LC-MS. Blood samples were collected from 8 horses for determination of TxB(2) and PGE(2) concentrations prior to and up to 96 h postflunixin administration. Mean systemic clearance, steady-state volume of distribution and terminal elimination half-life was 0.767 ± 0.098 mL/min/kg, 0.137 ± 0.12 L/kg, and 4.8 ± 1.59 h, respectively. Four of the 16 horses had serum concentrations in excess of the current ARCI recommended regulatory threshold at 24 h postadministration. TxB(2) suppression was significant for up to 24 h postadministration.
© 2015 John Wiley & Sons Ltd.
Publication Date: 2015-01-13 PubMed ID: 25582761DOI: 10.1111/jvp.12197Google Scholar: Lookup
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- Clinical Trial
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research paper examines the pharmacokinetic properties and effects of flunixin meglumine in horses related to thromboxane B2 production, specifically how it behaves in the body, including its absorption, distribution, metabolism, and excretion. The paper suggests that current regulatory standards on its usage might need to be revised.
Research Objectives
- The study aimed to update our understanding of the pharmacokinetics of flunixin meglumine in horses after an intravenous administration. This was done by using a modern and highly sensitive method: the liquid chromatography-mass spectrometry (LC-MS).
- Another aim was to characterize the effects of flunixin meglumine on the inhibition of COX-1 and COX-2 enzymes when the drug concentration reached the current recommended regulatory threshold.
Methods
- The study involved sixteen adult horses that had undergone exercise. They were given a single intravenous dose of flunixin meglumine (1.1 mg/kg).
- Blood samples were collected from these horses up to 72 hours after the administration of the drug, and subsequently analyzed using LC-MS.
- Blood samples were also collected from eight horses, before and up to 96 hours after the administration of the drug. These samples were specifically used to study TxB(2) and PGE(2) concentrations.
Results
- The researchers found results related to the systemic clearance, steady-state volume of distribution, and the terminal elimination half-life of the drug.
- A significant finding was that four out of the sixteen horses showed serum concentrations more than the current recommended regulatory threshold 24 hours after being given the drug. This could suggest that the current regulatory standard might be too low.
- The suppression of TxB(2) was found to be significant up to 24 hours after the administration of the drug.
This research contributes to the understanding of the pharmacokinetics of the drug flunixin meglumine in horses and its effect on TxB(2) production. The study suggests that adjustments might be needed to the current regulatory standards for its usage especially as some samples exceeded the regulatory threshold 24 hours post-administration.
Cite This Article
APA
Knych HK, Arthur RM, McKemie DS, Chapman N.
(2015).
Pharmacokinetics and effects on thromboxane B2 production following intravenous administration of flunixin meglumine to exercised thoroughbred horses.
J Vet Pharmacol Ther, 38(4), 313-320.
https://doi.org/10.1111/jvp.12197 Publication
Researcher Affiliations
- K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
- Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
- School of Veterinary Medicine, University of California, Davis, CA, USA.
- K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
- K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
MeSH Terms
- Animals
- Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
- Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
- Anti-Inflammatory Agents, Non-Steroidal / pharmacology
- Area Under Curve
- Clonixin / administration & dosage
- Clonixin / analogs & derivatives
- Clonixin / pharmacokinetics
- Clonixin / pharmacology
- Female
- Half-Life
- Horses / blood
- Horses / metabolism
- Injections, Intravenous
- Male
- Physical Exertion / physiology
- Thromboxane B2 / metabolism
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