Pharmacokinetics of flunixin meglumine in lactating cattle after single and multiple intramuscular and intravenous administrations

Abstract

SUMMARY The pharmacokinetics of flunixin were studied in 6 adult lactating cattle after administration of single iv and im doses at 1.1 mg/kg of body weight. A crossover design was used, with route of first administration in each cow determined randomly. Plasma and milk concentrations of total flunixin were determined by use of high-pressure liquid chromatography, using an assay with a lower limit of detection of 50 ng of flunixin/ml. The pharmacokinetics of flunixin were best described by a 2-compartment, open model. After iv administration, mean plasma flunixin concentrations rapidly decreased from initial concentrations of > 10 μg/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t½α, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t½β, harmonic mean = 3.14 hours). Mean ± sd clearance after iv administration was 2.51 ± 0.96 ml/kg/min. After im administration, the harmonic mean for the elimination phase (t½β) was prolonged at 5.20 hours. Bioavailability after im dosing gave a mean ± sd (n = 5) of 76.0 ± 28.0%. Adult, lactating cows (n = 6) were challenge inoculated with endotoxin as a model of acute coliform mastitis. After multiple administration (total of 7 doses; first iv, remainder im) of 1.1 mg/kg doses of flunixin at 8-hour intervals, plasma flunixin concentrations were approximately 1 μg/ml at 2 hours after each dosing and 0.5 μg/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study. Flunixin concentrations necessary to induce therapeutic effects in cattle are unknown. Results of our study indicate that administration of 1.1 mg/kg doses of flunixin meglumine at 8-hour intervals would produce plasma concentrations similar to those demonstrated to be effective clinically in treatment of equine musculoskeletal disorders and colic.