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

Previous work has shown repeated low doses of flunixin meglumine (FM) inhibit thromboxane production in normal horses. Enhanced concentrations of thromboxane in serum occurred after the drug therapy was discontinued. Our study was performed to evaluate the effects of low doses of FM in horses repeatedly challenged with endotoxin. Group I horses received E. coli endotoxin (0.1 μ g/kg IV) at 0 and 90 h. Group II horses received endotoxin and were also treated with FM (0.25 mg/kg IV) at 2, 10, 18, 26, 34, and 42 h after the initial administration of endotoxin. Clinical signs of endotoxemia were observed in all horses, but FM treated horses recovered more rapidly. The leukopenic response after endotoxin was attenuated in Group II following the second dose. Serum thromboxane (TxB 2) decreased after the initial administration of endotoxin and remained below baseline values throughout the study. Serum TxB 2 concentrations were not different between the groups. Plasma TxB 2 and 6-keto-PGF 2α concentrations were increased after the initial endotoxin injection. In Group II, plasma TxB 2 levels declined rapidly after FM administration and remained low. After the second dose of endotoxin, Group I horses had a mild rise and decline in TxB 2 and 6-keto-PGF 2α concentrations, respectively. Thromboxane B 2 levels in Group II changed little after the second dose of endotoxin, but a dramatic increase in 6-keto-PGF 2α concentrations occurred. These results suggest that multiple low doses of FM to horses with endotoxemia cause a selective and sustained suppression of TxB 2 production and an enhancement of 6-keto-PGF 2α.