Pharmacokinetics

Flunixin meglumine is a weak acid which exhibits a high degree of plasma protein binding (approximately 99%). However, free (unbound) drug appears to readily partition into body tissues. In cattle, elimination occurs primarily through biliary (liver) excretion. Several authors have reported different kinetic norms for cattle. One item for certain is that the half life in cattle (3.0 to 5.0 hours) is considerably longer than in the horse (1.6 hours). Additionally, flunixin tends to be sequestered at the site of inflammation, making dosing decisions based on plasma levels inaccurate. They underestimate both the duration of drug action and the concentration of drug remaining at the site of activity.

Target Animal Safety

Safety was accessed in 24 Hereford calves (12 male and 12 female) 5 to 6 months of age. Doses were 0, 1X, 3X and 5X the recommended 2.2 mg/kg given intravenously once daily for 9 consecutive days. There were 3 male and 3 female animals in each treatment group. Results were:

• Water consumption — no treatment related effects were observed.
• Feed consumption — slightly decreased feed consumption was observed in the 6.6 and 11.0 mg/kg groups.
• Hematology/Serum Chemistry — no treatment related effects were observed.
• Gross and Histopathology — no treatment related effects were observed.
• Clinical observations — clinically-observed fecal blood was the only treatment-related change seen sporadically in the 6.6 and 11.0 mg/kg groups. In the 6.6 mg/kg group, 4 different animals had fecal blood on one day only ranging from Day 3 to Day 9. In the 11 mg/kg group, 5 animals had at least one day of fecal blood, with only 2 animals exhibiting it for more than one day.
• Fecal examinations — slightly increased incidence of frank and/or occult blood in the 6.6 and 11 mg/kg groups were observed.
• Urinalysis — slightly increased incidence of microscopic RBC's and/or occult blood in the 6.6 and 11 mg/kg groups were observed.

In conclusion, adverse clinical signs attributed to flunixin intravenous injections were seen in calves administered elevated doses of 6.6 and 11 mg/kg, 3 and 5 times the high end of the recommended dose range, for 3 times the recommended clinical duration. No adverse effects were seen in calves given the high end of the recommended dose range (2.2 mg/kg).