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.
Objective—To determine the elimination kinetics of
ceftiofur hydrochloride in milk after intramammary
administration in lactating dairy cows.
Animals—5 lactating dairy cows.
Procedure—After collection of baseline milk samples,
300 mg (6 mL) of ceftiofur was infused into the
left front and right rear mammary gland quarters of
each cow. Approximately 12 hours later, an additional
300 mg of ceftiofur was administered into the
same mammary gland quarters after milking. Milk
samples were collected from each mammary gland
quarter every 12 hours for 10 days. Concentrations of
ceftiofur and its metabolites in each milk sample
were determined to assess the rate of ceftiofur elimination.
Results—Although there were considerable variations
among mammary gland quarters and individual
cows, ceftiofur concentrations in milk from all treated
mammary gland quarters were less than the tolerance
(0.1 µg/mL) set by the FDA by 168 hours (7 days)
after the last intramammary administration of ceftiofur.
No drug concentrations were detected in milk
samples beyond this period. Ceftiofur was not detected
in any milk samples from nontreated mammary
gland quarters throughout the study.
Conclusions and Clinical Relevance—Ceftiofur
administered by the intramammary route as an extralabel
treatment for mastitis in dairy cows reaches
concentrations in milk greater than the tolerance set
by the FDA. Results indicated that milk from treated
mammary gland quarters should be discarded for a
minimum of 7 days after intramammary administration
of ceftiofur. Elimination of ceftiofur may be correlated
with milk production, and cows producing smaller
volumes of milk may have prolonged withdrawal
times. (J Am Vet Med Assoc 2004;224:1827–1830)
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.