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Comparison of pharmacokinetics and milk elimination of flunixin in healthy cows and cows with mastitis

Lindsey W. KissellDepartment of Population Health and Pathobiology and the Food Animal Residue Avoidance Databank, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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Teresa L. LeavensPharmacokinetics Consulting, Cary, NC 27513.

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Ronald E. BaynesDepartment of Population Health and Pathobiology and the Food Animal Residue Avoidance Databank, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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Jim E. RiviereDepartment of Anatomy and Physiology and the Food Animal Residue Avoidance Databank, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66505.

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Geof W. SmithDepartment of Population Health and Pathobiology and the Food Animal Residue Avoidance Databank, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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Abstract

Objective—To determine whether pharmacokinetics and milk elimination of flunixin and 5-hydroxy flunixin differed between healthy and mastitic cows.

Design—Prospective controlled clinical trial.

Animals—20 lactating Holstein cows.

Procedures—Cows with mastitis and matched control cows received flunixin IV, ceftiofur IM, and cephapirin or ceftiofur, intramammary. Blood samples were collected before (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours after flunixin administration. Composite milk samples were collected at 0, 2, 12, 24, 36, 48, 60, 72, 84, and 96 hours. Plasma and milk samples were analyzed by use of ultra–high-performance liquid chromatography with mass spectrometric detection.

Results—For flunixin in plasma samples, differences in area under the concentration-time curve and clearance were detected between groups. Differences in flunixin and 5-hydroxy flunixin concentrations in milk were detected at various time points. At 36 hours after flunixin administration (milk withdrawal time), 8 cows with mastitis had 5-hydroxy flunixin concentrations higher than the tolerance limit (ie, residues). Flunixin residues persisted in milk up to 60 hours after administration in 3 of 10 mastitic cows.

Conclusions and Clinical Relevance—Pharmacokinetics and elimination of flunixin and 5-hydroxy flunixin in milk differed between mastitic and healthy cows, resulting in violative residues. This may partially explain the high number of flunixin residues reported in beef and dairy cattle. This study also raised questions as to whether healthy animals should be used when determining withdrawal times for meat and milk.

Abstract

Objective—To determine whether pharmacokinetics and milk elimination of flunixin and 5-hydroxy flunixin differed between healthy and mastitic cows.

Design—Prospective controlled clinical trial.

Animals—20 lactating Holstein cows.

Procedures—Cows with mastitis and matched control cows received flunixin IV, ceftiofur IM, and cephapirin or ceftiofur, intramammary. Blood samples were collected before (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, 24, and 36 hours after flunixin administration. Composite milk samples were collected at 0, 2, 12, 24, 36, 48, 60, 72, 84, and 96 hours. Plasma and milk samples were analyzed by use of ultra–high-performance liquid chromatography with mass spectrometric detection.

Results—For flunixin in plasma samples, differences in area under the concentration-time curve and clearance were detected between groups. Differences in flunixin and 5-hydroxy flunixin concentrations in milk were detected at various time points. At 36 hours after flunixin administration (milk withdrawal time), 8 cows with mastitis had 5-hydroxy flunixin concentrations higher than the tolerance limit (ie, residues). Flunixin residues persisted in milk up to 60 hours after administration in 3 of 10 mastitic cows.

Conclusions and Clinical Relevance—Pharmacokinetics and elimination of flunixin and 5-hydroxy flunixin in milk differed between mastitic and healthy cows, resulting in violative residues. This may partially explain the high number of flunixin residues reported in beef and dairy cattle. This study also raised questions as to whether healthy animals should be used when determining withdrawal times for meat and milk.

Contributor Notes

Supported by the Food Animal Residue and Avoidance and Depletion Program.

Presented in abstract form at the American Academy of Veterinary Pharmacology and Therapeutics Biennial Symposium, Potomac, Md, May 2013.

Address correspondence to Dr. Kissell (lwaltma@ncsu.edu).