Pharmacokinetics and tissue elimination of flunixin in veal calves

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.

Characterization, Source and Risk of Pharmaceutically Active Compounds (PhACs) in the Snow Deposition Near Jiaozhou Bay, North China

“…The results showed that PC1 was a factor of human drugs [62,63]. The second principal component (PC2) explained 17.97% of total variance, corresponding to the high loads of the veterinary drugs of flunixin, sulfamethoxazole, and tetracycline [64,65]. The third principal component (PC3) explained 14.94% of total variance, corresponding to the high loads of 5-nitrobenzimidazole, oxolinic acid, 5-chloto-1-methyl-4-nitroimidazole, and roxithromycin.…”

Considerations for extralabel drug use in calves

“…In fact, there is considerable ongoing research in both human and veterinary medicine on the effects of organ development on drug metabolism and elimination. Results of multiple pharmacokinetic studies [10][11][12][13][14][15][16] indicate that the plasma elimination half-life, clearance rate, and volume of distribution for many drugs vary substantially between calves and adult cattle. Veterinarians should also be cognizant that plasma pharmacokinetic parameters do not necessarily accurately reflect drug dynamics in organs and tissues.…”

“…[53][54][55] From October 2013 through September 2014, the FSIS identified residue violations in 1,146 animals processed in US slaughter houses, of which 108 (10%) were caused by flunixin; 17 of the 108 (16%) animals with violative flunixin residues were immature cattle (veal calves [n = 9] and heavy calves [ruminating animals typically slaughtered at > 182 kg {400 lb}; 8]). 38 In 1 study, 11 veal calves administered flunixin (2.2 mg/kg [1 mg/lb], IV, q 24 h for 3 days [ie, the labeled dosage for adult cattle]) had detectable concentrations of that drug in both liver and muscle tissue for at least 5 days after injection of the last dose. Flunixin is a drug of high regulatory concern for the FDA.…”

“…the clearance and tissue elimination half-life of flunixin are dependent on the age and disease status of the treated animal, FARAD recommends a meat WDI of at least 14 days when flunixin is administered in accordance with the labeled dosage to dairy heifer, beef steer, and veal calves. 11 Further information regarding the avoidance of flunixin residues in cattle is available in a previous FARAD Digest. 56…”

Pharmacokinetic Parameters and Estimated Milk Withdrawal Intervals for Domestic Goats (Capra Aegagrus Hircus) After Administration of Single and Multiple Intravenous and Subcutaneous Doses of Flunixin Meglumine

“…Practical use of FM becomes problematic for veterinarians treating minor food-producing species (such as dairy goats) as they must often extrapolate milk withholding intervals based on cattle data in order to avoid drug residues in caprine milk. The extra-label use of FM can result in prolonged detectable drug residues in animal-derived food products such as veal destined for human consumption (13). Drug residue problems are not limited to meat, as FLU metabolite residues found in bovine milk are some of the most common violations (4).…”