Pharmacokinetics of flunixin meglumine in lactating cattle after single and multiple intramuscular and intravenous administrations.
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 greater than 10 micrograms/ml to nondetectable concentrations at 12 hours after administration. The distribution phase was short (t1/2 alpha, harmonic mean = 0.16 hours) and the elimination phase was more prolonged (t1/2 beta, 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 (t1/2 beta) 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 microgram/ml at 2 hours after each dosing and 0.5 micrograms/ml just prior to each dosing. Flunixin was not detected in milk at any sampling during the study.(ABSTRACT TRUNCATED AT 250 WORDS)
Anderson
K L
KL
Department of Food Animal and Equine Medicine, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Neff-Davis
C A
CA
Davis
L E
LE
Bass
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VD
D000818:Animals; D002417:Cattle / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D003002:Clonixin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule / Q000662:veterinary; D005260:Female; D006207:Half-Life; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D007774:Lactation; D008657:Metabolic Clearance Rate; D008892:Milk / Q000032:analysis; D009539:Nicotinic Acids / Q000493:pharmacokinetics*; D011897:Random Allocation; D013997:Time Factors
D009539:Nicotinic Acids; C014558:flunixin meglumine; D003002:Clonixin