Flunixin Residues in Milk after Intravenous Treatment of Dairy Cattle with ¹⁴C-Flunixin

Abstract

Flunixin meglumine is used in veterinary medicine as an alternative to narcotic analgesics and as an antiinflammatory agent. Eight Holstein dairy cows were dosed intravenously once daily on three consecutive days with (14)C-flunixin meglumine at approximately 2.2 mg of flunixin free acid/kg of body weight. Milk was collected twice daily to determine the decline of the total radioactive residues (TRR) in milk and to identify or characterize residue components. TRR in milk declined rapidly and averaged 66, 20, and 14 ppb, respectively, for the first, second, and third milkings after administration of the last dose. Milk was extracted, and the extracts were examined for radioactive residues. Mean extractability of milk TRR was always greater than 80%. Flunixin and 5-hydroxyflunixin were identified by coelution with analytical standards using reverse phase HPLC. These two residues were the main radioactive residues found in milk and together accounted for 64, 37, and 44% of the extractable residues, for the first, second, and third milkings, respectively, after administration of the last dose. The presence of 5-OH flunixin in milk was confirmed by HPLC/MS/MS.

Identification of flunixin glucuronide and depletion of flunixin and its marker residue in bovine milk

“…These results are in good agreement with data published by Feely et al . () and Ngoh et al . (), who found 32 or 20 μg/kg of 5OHFLU in milk samples during the first milking.…”

“…Feely et al . () determined FLU with a mean concentration of 12 μg/kg in the milk samples collected in the first milking, whereas FLU level determined by Daeseleire et al . was 4.4 μg/kg (2003).…”

Excretory, Secretory, and Tissue Residues after Label and Extra-label Administration of Flunixin Meglumine to Saline- or Lipopolysaccharide-Exposed Dairy Cows

“…Similarly, 5OHF exceeded 2 ng/mL 36 h after the last flunixin dose in 25% of the eight cattle studied by Feely et al 27 and in 8 of 20 cattle studied by Kissell et al 10 With a 48 h withdrawal time, 2 of the 20 animals (10%) in the present study had 5OHF levels greater than allowable under U.S. statutory limits: a single cow from the iv-flunixin (−)LPS group (label conditions; cow 1) and a single cow from the im-flunixin (+)LPS group (off-label conditions; cow 18). Again, this result does not seem remarkable given the fact that of the eight cows dosed by Feely et al, 27 a single cow secreted 17 ng/g of total radioactive residue (TRR) after a 48 h withdrawal period; assuming that 5OHF represented 20% of the total TRR in this milk, 5OHF would have exceeded tolerance levels at 3.4 ng/mL. In recent studies, Kissell et al 9 measured violative 5OHF levels in milk of two cows 36 h after the last im or subcutaneous flunixin administration, but residues were not present at a 48 h withdrawal time.…”

In-house reference materials: 5-hydroxyflunixin and meloxicam in cow milk—preparation and evaluation

“…It means that 12 h after last injection (when milk was collected) not all flunixin excreted to milk was metabolised to its marker residue. The presence of 5OHFLU and FLU in incurred milk was described by Feely et al [17] and Daeseleire et al [18]. However, Rupp et al [19] suggest FLU can be partly conjugated with glucuronic acid.…”