Flunixin meglumine given in small doses: pharmacokinetics and prostaglandin inhibition in healthy horses.
Abstract: The pharmacokinetics and inhibition of prostaglandin synthesis in conscious horses given various dosages of flunixin meglumine were studied. Plasma concentrations of flunixin were measured by high-performance liquid chromatography, and serum thromboxane B2 and 6-keto prostaglandin F1 alpha were quantitated by radioimmunoassay. Within the dosage range studied, linear pharmacokinetics were achieved. After IV administration of flunixin (1.1 mg/kg, 0.25 mg/kg, 0.1 mg/kg), significant suppression of serum thromboxane generation persisted for 12, 4, and 3 hours, respectively. Repeated administrations of flunixin (0.25 mg/kg) once every 8 hours maintained significant suppression of thromboxane generation for the duration of treatment. After treatment with flunixin was stopped, serum thromboxane generation exceeded base line (pretreatment values). Among the groups, significant alteration of 6-keto prostaglandin F1 alpha production was not observed.
Publication Date: 1985-12-01 PubMed ID: 4083579
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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The researchers investigated the effects and behaviour of different doses of flunixin meglumine, a non-steroidal anti-inflammatory drug (NSAID), in horses in terms of how long it remains in the body and its impact on prostaglandin, a group of lipids that play a key role in the body’s inflammatory responses.
Research Methodology
- The study used healthy horses as test subjects and administered varying doses of flunixin meglumine.
- Researchers utilized high-performance liquid chromatography, a method used in biochemistry and analytical chemistry to identify, quantify and purify individual components of a mixture to measure plasma concentrations of flunixin.
- The quantities of serum thromboxane B2 and 6-keto prostaglandin F1 alpha, compounds involved in inflammatory responses, were determined through radioimmunoassay, a technique used to measure antigens.
Main Findings
- The pharmacokinetics, or how the drug is absorbed, distributed, metabolised, and excreted, of flunixin showed linear characteristics within the dosage range studied. This implies that the behaviour of the drug in the body is predictable and proportional to the dose administered.
- There was significant suppression of serum thromboxane production for different time frames depending on the dose of flunixin given intravenous (IV) – 12 hours for 1.1 mg/kg, 4 hours for 0.25 mg/kg, and 3 hours for 0.1 mg/kg.
- When the flunixin was administered repeatedly at the dose of 0.25 mg/kg every 8 hours, the suppression of thromboxane production was sustained throughout the treatment.
- However, after ceasing the flunixin treatment, serum thromboxane production exceeded the pretreatment levels.
- The researchers found no significant changes in the production of 6-keto prostaglandin F1 alpha among the groups.
Conclusions
- The study demonstrated how the body processes flunixin meglumine in horses, showing a direct relationship between the administered dose and the drug’s behaviour in the body.
- The treatment also had a clear impact on inflammatory pathways by suppressing thromboxane generation, but this suppression in thromboxane production was not maintained once the treatment ceased.
- The lack of alteration in 6-keto prostaglandin F1 alpha production indicates that the effects of flunixin are not universal for all prostaglandins.
Implications
- The findings shed light on optimal dosing strategies for flunixin meglumine in horses and the drug’s potential consequences on the body’s inflammatory responses.
- This kind of information may be of interest to veterinarians and pharmaceutical scientists for designing better medication regimens for horse patients and possibly developing improvements to the drug.
Cite This Article
APA
Semrad SD, Hardee GE, Hardee MM, Moore JN.
(1985).
Flunixin meglumine given in small doses: pharmacokinetics and prostaglandin inhibition in healthy horses.
Am J Vet Res, 46(12), 2474-2479.
Publication
Researcher Affiliations
MeSH Terms
- Animals
- Clonixin / administration & dosage
- Clonixin / analogs & derivatives
- Clonixin / blood
- Horses
- Kinetics
- Nicotinic Acids / blood
- Prostaglandin Antagonists / administration & dosage
- Prostaglandin Antagonists / blood
- Thromboxane B2 / blood
Citations
This article has been cited 6 times.- Vernemmen I, Buschmann E, Van Steenkiste G, Demeyere M, Verhaeghe LM, De Somer F, Devreese KMJ, Schauvliege S, Decloedt A, van Loon G. Intracardiac ultrasound-guided transseptal puncture in horses: Outcome, follow-up, and perioperative anticoagulant treatment. J Vet Intern Med 2024 Sep-Oct;38(5):2707-2717.
- Ziegler AL, Blikslager AT. Sparing the gut: COX-2 inhibitors herald a new era for treatment of horses with surgical colic. Equine Vet Educ 2020 Nov;32(11):611-616.
- . Poster communications. Br J Pharmacol 1993 Jul;109(Suppl):67P-142P.
- Cheng Z, McKellar Q, Nolan A, Lees P. Preliminary pharmacokinetic and pharmacodynamic studies on flunixin meglumine in donkeys. Vet Res Commun 1996;20(5):469-72.
- Jackman BR, Moore JN, Barton MH, Morris DD. Comparison of the effects of ketoprofen and flunixin meglumine on the in vitro response of equine peripheral blood monocytes to bacterial endotoxin. Can J Vet Res 1994 Apr;58(2):138-43.
- Kinabo LD, McKellar QA. Current models in pharmacokinetics: applications in veterinary pharmacology. Vet Res Commun 1989;13(2):141-57.
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