Effects of multiple low doses of flunixin meglumine on repeated endotoxin challenge in the horse.

This research investigates the effects of administering multiple low doses of flunixin meglumine, a non-steroidal anti-inflammatory drug, on horses that have been repeatedly exposed to endotoxin. The study found that the treatment rapidly aided recovery, selectively and sustainably suppressed thromboxane production, and increased 6-keto-prostaglandin F1 alpha concentration in the serum.

Study Design and Methodology

• The study was conducted with two sets of horses, Group I and Group II, that were all exposed to E. coli endotoxin. This type of endotoxin is a harmful substance produced by bacteria.
• Group I horses received only endotoxin while Group II horses received both endotoxin and flunixin meglumine at predetermined intervals after initial endotoxin administration.

Observations and Findings

• Both groups of horses showed clinical signs of endotoxemia, a systemic inflammatory response to endotoxins commonly seen in horses. However, horses treated with flunixin meglumine in Group II recovered more quickly.
• The effect of endotoxin on the white blood cell count was less severe in Group II horses after receiving the second dose.
• The level of thromboxane, a substance that promotes platelet aggregation and blood clotting, dropped after the initial dose of the endotoxin and remained below baseline values throughout the study for both groups of horses.
• There was an increase of thromboxane and 6-keto-prostaglandin F1 alpha, an anti-inflammatory hormone, in plasma after initial endotoxin administration. In Group II horses, thromboxane levels dropped rapidly after administration of flunixin meglumine and stayed low.
• After the second dose of endotoxin, the level of thromboxane in Group I horses slightly rose and then declined while the concentration of 6-keto-PGF1 alpha decreased. In contrast, there was a little change in thromboxane levels in Group II horses after second endotoxin administration, but 6-keto-PGF1 alpha concentrations rose sharply.

Conclusion

• These observations suggest that administering multiple low doses of flunixin meglumine to horses suffering from endotoxemia can selectively and sustainably suppress thromboxane production. At the same time, it enhances the production of 6-keto-PGF1 alpha, aiding in the recovery process from inflammation induced by endotoxin.