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Pharmacokinetics and tissue elimination of flunixin in veal calves

Lindsey W. Kissell DVM, PhD1, Patrick D. Brinson DVM2, Ronette Gehring BVSc, MMED VET3, Lisa A. Tell DVM4, Scott E. Wetzlich BS5, Ronald E. Baynes DVM, PhD6, Jim E. Riviere DVM, PhD7, and Geof W. Smith DVM, PhD8
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  • 1 Department of Population Health and Pathobiology, College of Veterinary Medicine, and Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC 27607.
  • | 2 Department of Population Health and Pathobiology, College of Veterinary Medicine, and Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC 27607.
  • | 3 Department of Anatomy and Physiology, College of Veterinary Medicine, and the Institute of Computational Comparative Medicine, Kansas State University, Manhattan, KS 66506.
  • | 4 Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 5 Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.
  • | 6 Department of Population Health and Pathobiology, College of Veterinary Medicine, and Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC 27607.
  • | 7 Department of Anatomy and Physiology, College of Veterinary Medicine, and the Institute of Computational Comparative Medicine, Kansas State University, Manhattan, KS 66506.
  • | 8 Department of Population Health and Pathobiology, College of Veterinary Medicine, and Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, Raleigh, NC 27607.

Abstract

OBJECTIVE To describe plasma pharmacokinetic parameters and tissue elimination of flunixin in veal calves.

ANIMALS 20 unweaned Holstein calves between 3 and 6 weeks old.

PROCEDURES Each calf received flunixin (2.2 mg/kg, IV, q 24 h) for 3 days. Blood samples were collected from all calves before the first dose and at predetermined times after the first and last doses. Beginning 24 hours after injection of the last dose, 4 calves were euthanized each day for 5 days. Plasma and tissue samples were analyzed by ultraperformance liquid chromatography. Pharmacokinetic parameters were calculated by compartmental and noncompartmental methods.

RESULTS Mean ± SD plasma flunixin elimination half-life, residence time, and clearance were 1.32 ± 0.94 hours, 12.54 ± 10.96 hours, and 64.6 ± 40.7 mL/h/kg, respectively. Mean hepatic and muscle flunixin concentrations decreased to below FDA-established tolerance limits (0.125 and 0.025 μg/mL, respectively) for adult cattle by 3 and 2 days, respectively, after injection of the last dose of flunixin. Detectable flunixin concentrations were present in both the liver and muscle for at least 5 days after injection of the last dose.

CONCLUSIONS AND CLINICAL RELEVANCE The labeled slaughter withdrawal interval for flunixin in adult cattle is 4 days. Because administration of flunixin to veal calves represents extralabel drug use, any detectable flunixin concentrations in edible tissues are considered a violation. Results indicated that a slaughter withdrawal interval of several weeks may be necessary to ensure that violative tissue residues of flunixin are not detected in veal calves treated with that drug.

Abstract

OBJECTIVE To describe plasma pharmacokinetic parameters and tissue elimination of flunixin in veal calves.

ANIMALS 20 unweaned Holstein calves between 3 and 6 weeks old.

PROCEDURES Each calf received flunixin (2.2 mg/kg, IV, q 24 h) for 3 days. Blood samples were collected from all calves before the first dose and at predetermined times after the first and last doses. Beginning 24 hours after injection of the last dose, 4 calves were euthanized each day for 5 days. Plasma and tissue samples were analyzed by ultraperformance liquid chromatography. Pharmacokinetic parameters were calculated by compartmental and noncompartmental methods.

RESULTS Mean ± SD plasma flunixin elimination half-life, residence time, and clearance were 1.32 ± 0.94 hours, 12.54 ± 10.96 hours, and 64.6 ± 40.7 mL/h/kg, respectively. Mean hepatic and muscle flunixin concentrations decreased to below FDA-established tolerance limits (0.125 and 0.025 μg/mL, respectively) for adult cattle by 3 and 2 days, respectively, after injection of the last dose of flunixin. Detectable flunixin concentrations were present in both the liver and muscle for at least 5 days after injection of the last dose.

CONCLUSIONS AND CLINICAL RELEVANCE The labeled slaughter withdrawal interval for flunixin in adult cattle is 4 days. Because administration of flunixin to veal calves represents extralabel drug use, any detectable flunixin concentrations in edible tissues are considered a violation. Results indicated that a slaughter withdrawal interval of several weeks may be necessary to ensure that violative tissue residues of flunixin are not detected in veal calves treated with that drug.

Contributor Notes

Dr. Kissell's present address is Merck Animal Health, 2 Giralda Farms, Madison, NJ 07940.

Dr. Brinson's present address is Lander Veterinary Clinic, 4512 S Walnut Rd, Turlock, CA 95380.

Address correspondence to Dr. Smith (Geoffrey_Smith@ncsu.edu).