ATCvet code: QM01AG90
Pharmacodynamics
Flunixin meglumine is a non-steroidal anti-inflammatory drug with analgesic and antipyretic activity. Flunixin meglumine acts as a reversible non-selective inhibitor of cyclo-oxygenase (both COX 1 and COX 2 forms), an enzyme in the arachidonic acid cascade pathway which is responsible for converting arachidonic acid to cyclic endoperoxides. Consequently, synthesis of eicosanoids, important mediators of the inflammatory process involved in central pyresis, pain perception and tissue inflammation are reduced. Through its effects on the arachidonic acid cascade, flunixin also inhibits the production of thromboxane, a potent platelet pro-aggregator and vasoconstrictor which is released during blood clotting. Flunixin exerts its antipyretic effect by inhibiting prostaglandin E2 synthesis in the hypothalamus. Although flunixin has no direct effect on endotoxins after they have been produced, it reduces prostaglandin production and hence reduces the many effects of the prostaglandin cascade. Prostaglandins are part of the complex processes involved in the development of endotoxic shock.
Due to the involvement of prostaglandins in other physiological processes, COX inhibition would also be responsible for different adverse reactions, such as gastrointestinal or renal damage.
Pharmacokinetic particulars
Following intravenous administration of flunixin meglumine to equines (horses and ponies) at a dose of 1.1 mg/kg, the drug kinetics fit a two-compartment model. It showed a rapid distribution (volume of distribution 0.16 l/kg), with a high proportion of binding to plasma proteins (greater than 99%). The elimination half-life was between 1 and 2 hours. An AUC0-15h of 19.43 μg·h/ml was determined. The excretion took place rapidly, mainly through the urine, reaching the maximum concentration therein 2 hours after administration.
After 12 hours of intravenous injection, 61% of the administered dose had been recovered in the urine.
In cattle, after administering a dose of 2.2 mg/kg intravenously, maximum plasma levels of between 15 and 18 μg/ml were obtained 5-10 minutes after injection. Between 2 and 4 hours later, a second plasma concentration peak was observed (possibly due to enterohepatic circulation), while at 24 hours the concentrations were less than 0.1 μg/ml. In cattle, after intramuscular administration of flunixin at a dose of 2 mg/kg, a maximum concentration is observed approximately 30 minutes after injection.
Flunixin meglumine is rapidly distributed into organs and body fluids (with high persistence in inflammatory exudate), with a volume of distribution between 0.7 and 2.3 l/kg. The elimination half-life was approximately 4 to 7 hours. Regarding excretion, this took place mainly through urine and feces. In milk, the drug was not detected, and in the cases where it was detected, the levels were negligible (<10 ng/ml).
In pigs, following intramuscular administration of 2.2 mg/kg flunixin meglumine, a maximum plasma concentration of about 3 μg/ml was detected approximately 20 minutes after injection.
The bioavailability, expressed as a fraction of the absorbed dose, was found to be 93%. The
Volume of distribution was 2 l/kg, while the elimination half-life was 3.6 hours. Excretion (most as unchanged drug) occurred primarily in the urine, although was also detected in the faeces.
Environmental properties
Flunixin is toxic to avian scavengers although foreseen low exposure leads to low risk.