Objective—To compare the results of regulatory
screening and confirmation assays with those of highperformance
liquid chromatography (HPLC) in the
detection of ceftiofur metabolites in the tissues of
culled dairy cattle.
Animals—17 lactating Holstein dairy cows.
Procedure—Daily IM injections of ceftiofur sodium
were administered at a dose of 2.2 mg of ceftiofur
equivalents/kg (n = 6) or 1.0 mg of ceftiofur equivalents/kg (10) for 5 days. Following withdrawal times of
12 hours (high-dose ceftiofur) and either 5 or 10 days
(low-dose ceftiofur), cows were slaughtered and liver,
kidney, and diaphragmatic muscle specimens were
harvested and analyzed by HPLC and standard regulatory
methods that included the following assays:
the swab test on premises, the fast antimicrobial
screen test, the calf antibiotic and sulfa test, and the
7-plate bioassay confirmation test.
Results—In all tissue specimens, residues of ceftiofur
and desfuroylceftiofur-related metabolites, as
measured by HPLC, were less than regulatory tolerance,
as defined by the FDA. False-positive screening
assay results were more likely for tissue specimens
that had been frozen for shipment to a federal laboratory,
compared with fresh tissue specimens that
were assayed at the slaughter establishment (23% vs
3% false-positive results, respectively).
Conclusions and Clinical Relevance—The observation
that fresh tissues had negative results on screening
assays, whereas subsets of the same tissue specimens
had false-positive results on screening assays
following freezing, suggests that freezing and thawing
interferes with microbial inhibition-based regulatory
screening assays. (Am J Vet Res 2004;65:1730–1733)
Objective—To determine the pharmacokinetics of
ceftiofur sodium after IM and SC administration in
Animals—6 male and 4 female adult green iguanas.
Procedure—In a crossover design, 5 iguanas
received a single dose of ceftiofur sodium (5 mg/kg)
IM, and 5 iguanas received the same dose SC. Blood
samples were taken at 0, 20, and 40 minutes and 1,
2, 4, 8, 24, 48, and 72 hours after administration. After
a 10-week washout period, each iguana was given the
same dose via the reciprocal administration route,
and blood was collected in the same fashion.
Ceftiofur free-acid equivalents were measured via
high-performance liquid chromatography.
Results—The first phase intercepts were significantly
different between the 2 administration routes.
Mean maximum plasma concentration was significantly
higher with the IM (28.6 ± 8.0 µg/mL) than the
SC (18.6 ± 8.3 µg/mL) administration route. There
were no significant differences between terminal halflives
(harmonic mean via IM route, 15.7 ± 4.7 hours;
harmonic mean via SC route, 19.7 ± 6.7 hours) and
mean areas under the curve measured to the last
time point (IM route, 11,722 ± 7,907 µg·h/mL; SC
route, 12,143 ± 9,633 µg·h/mL). Ceftiofur free-acid
equivalent concentrations were maintained ≥ 2 µg/mL
for > 24 hours via both routes.
Conclusions and Clinical Relevance—A suggested
dosing schedule for ceftiofur sodium in green iguanas
for microbes susceptible at > 2 µg/mL would be 5
mg/kg, IM or SC, every 24 hours. (Am J Vet Res 2003;64:1278–1282)
Objective—To determine the tissue depletion profile of tulathromycin and determine an appropriate slaughter withdrawal interval in meat goats after multiple SC injections of the drug.
Animals—16 healthy Boer goats.
Procedures—All goats were administered tulathromycin (2.5 mg/kg, SC) twice, with a 7-day interval between doses. Blood samples were collected throughout the study, and goats were euthanized at 2, 5, 10, and 20 days after the second tulathromycin dose. Lung, liver, kidney, fat, and muscle tissues were collected. Concentrations of tulathromycin in plasma and the hydrolytic tulathromycin fragment CP-60,300 in tissue samples were determined with ultrahigh-pressure liquid chromatography–tandem mass spectrometry.
Results—The plasma profile of tulathromycin was biphasic. Absorption was very rapid, with maximum drug concentrations (1.00 ± 0.42 μg/mL and 2.09 ± 1.77 μg/mL following the first and second doses, respectively) detected within approximately 1 hour after injection. Plasma terminal elimination half-life of tulathromycin was 61.4 ± 14.1 hours after the second dose. Half-lives in tissue ranged from 2.4 days for muscle to 9.0 days for lung tissue; kidney tissue was used to determine the withdrawal interval for tulathromycin in goats because it is considered an edible tissue.
Conclusions and Clinical Relevance—On the basis of the tissue tolerance limit in cattle of 5 ppm (μg/g), the calculated withdrawal interval for tulathromycin would be 19 days following SC administration in goats. On the basis of the more stringent guidelines recommended by the FDA, the calculated meat withdrawal interval following tulathromycin administration in goats was 34 days.
Objective—To determine the pharmacokinetic properties of 1 IM injection of ceftiofur crystalline-free acid (CCFA) in American black ducks (Anas rubripes).
Animals—20 adult American black ducks (6 in a preliminary experiment and 14 in a primary experiment).
Procedures—Dose and route of administration of CCFA for the primary experiment were determined in a preliminary experiment. In the primary experiment, CCFA (10 mg/kg, IM) was administered to ducks. Ducks were allocated into 2 groups, and blood samples were obtained 0.25, 0.5, 1, 2, 4, 8, 12, 48, 96, 144, 192, and 240 hours or 0.25, 0.5, 1, 2, 4, 8, 24, 72, 120, 168, and 216 hours after administration of CCFA. Plasma concentrations of ceftiofur free acid equivalents (CFAEs) were determined by use of high-performance liquid chromatography. Data were evaluated by use of a naive pooled-data approach.
Results—The area under the plasma concentration versus time curve from 0 hours to infinity was 783 h•μg/mL, maximum plasma concentration observed was 13.1 μg/mL, time to maximum plasma concentration observed was 24 hours, terminal phase half-life was 32.0 hours, time that concentrations of CFAEs were higher than the minimum inhibitory concentration (1.0 μg/mL) for many pathogens of birds was 123 hours, and time that concentrations of CFAEs were higher than the target plasma concentration (4.0 μg/mL) was 73.3 hours.
Conclusions and Clinical Relevance—On the basis of the time that CFAE concentrations were higher than the target plasma concentration, a dosing interval of 3 days can be recommended for future multidose CCFA studies.
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.
Procedures—Each sheep was administered 6.6 mg of CCFA/kg, SC, in the cervical region once. Serial blood samples were collected at predetermined intervals for 14 days. Serum concentration of ceftiofur free-acid equivalents (CFAE) was determined by high-performance liquid chromatography. Pharmacokinetic parameters were determined by compartmental and noncompartmental methods.
Results—Pharmacokinetics for CCFA following SC administration in sheep was best described with a 1-compartment model. Mean ± SD area under the concentration-time curve from time 0 to infinity, peak serum concentration, and time to peak serum concentration were 206.6 ± 24.8 μ•h/mL, 2.4 ± 0.5 μg/mL, and 23.1 ± 10.1 h, respectively. Serum CFAE concentrations ≥ 1 μg/mL (the target serum CFAE concentration for treatment of disease caused by Mannheimia haemolytica and Pasteurella multocida) were maintained for 2.6 to 4.9 days. No significant adverse reactions to CCFA administration were observed.
Conclusions and Clinical Relevance—Results indicated that adequate therapeutic serum concentrations of CFAE for treatment of disease caused by M haemolytica and P multocida were achieved in sheep following SC administration of a single dose (6.6 mg/kg) of CCFA. Thus, CCFA might be useful for the treatment of common respiratory tract pathogens in sheep.
OBJECTIVE To compare the pharmacokinetics of 2 commercial florfenicol formulations following IM and SC administration to sheep.
ANIMALS 16 healthy adult mixed-breed sheep.
PROCEDURES In a crossover study, sheep were randomly assigned to receive florfenicol formulation A or B at a single dose of 20 mg/kg, IM, or 40 mg/kg, SC. After a 2-week washout period, each sheep was administered the opposite formulation at the same dose and administration route as the initial formulation. Blood samples were collected immediately before and at predetermined times for 24 hours after each florfenicol administration. Plasma florfenicol concentrations were determined by high-performance liquid chromatography. Pharmacokinetic parameters were estimated by noncompartmental methods and compared between the 2 formulations at each dose and route of administration.
RESULTS Median maximum plasma concentration, elimination half-life, and area under the concentration-time curve from time 0 to the last quantifiable measurement for florfenicol were 3.76 μg/mL, 13.44 hours, and 24.88 μg•h/mL, respectively, for formulation A and 7.72 μg/mL, 5.98 hours, and 41.53 μg•h/mL, respectively, for formulation B following administration of 20 mg of florfenicol/kg, IM, and 2.63 μg/mL, 12.48 hours, and 31.63 μg•h/mL, respectively, for formulation A and 4.70 μg/mL, 16.60 hours, and 48.32 μg•h/mL, respectively, for formulation B following administration of 40 mg of florfenicol/kg, SC.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that both formulations achieved plasma florfenicol concentrations expected to be therapeutic for respiratory tract disease caused by Mannheimia haemolytica or Pasteurella spp at both doses and administration routes evaluated.