ceftiofur and flunixin

To determine whether pharmacokinetics and milk elimination of flunixin and 5-hydroxy flunixin differed between healthy and mastitic cows.. Prospective controlled clinical trial.. 20 lactating Holstein cows.. 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.. 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.. 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.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Cephalosporins; Clonixin; Female; Mastitis, Bovine; Milk

Three non-steroidal anti-inflammatory drugs (NSAIDs), flunixin, ketoprofen and carprofen, were used in conjunction with ceftiofur, in the treatment of naturally occurring bovine respiratory disease. Sixty-six mixed-breed beef cattle weighing on average 197 kg met the inclusion criteria of pyrexia of at least 40 degrees C, an illness score indicating at least moderate illness and at least moderate dyspnoea. They were allocated randomly to four treatment groups. All the groups received ceftiofur for three days at a dose rate of 1.1 mg/kg by intramuscular injection, and three groups received, in addition, a single dose of either flunixin (2.2 mg/kg by intravenous injection) or ketoprofen (3 mg/kg by intravenous injection) or carprofen (1.4 mg/kg by subcutaneous injection). During the first 24 hours of the study, the pyrexia of the three groups treated with a NSAID was reduced significantly more than the pyrexia of the group treated with ceftiofur alone, and two and four hours after treatment the reduction in pyrexia was significantly greater in the groups treated with flunixin and ketoprofen than in the group treated with carprofen. There were no statistically significant differences between the four groups with respect to depression, illness scores, dyspnoea or coughing. There was less lung consolidation in the three groups treated with a NSAID than in the animals treated with ceftiofur alone, but the difference was significant only in the group treated with flunixin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Body Temperature; Carbazoles; Cephalosporins; Clonixin; Drug Therapy, Combination; Ketoprofen; Respiratory Tract Infections

There has been a lack of information about the inhibition of bovine medicines on bovine hepatic CYP450 at their commercial doses and dosing routes.. The aim of this work was to assess the inhibition of 43 bovine medicines on bovine hepatic CYP450 using a combination of in vitro assay and Cmax values from pharmacokinetic studies with their commercial doses and dosing routes in the literature.. Those drugs were first evaluated through a single point inhibitory assay at 3 μM in bovine liver microsomes for six specific CYP450 metabolisms, phenacetin o-deethylation, coumarin 7- hydroxylation, tolbutamide 4-hydroxylation, bufuralol 1-hydroxylation, chlorzoxazone 6-hydroxylation and midazolam 1'-hydroxylation. When the inhibition was greater than 20% in the assay, IC50 values were then determined. The potential in vivo bovine hepatic CYP450 inhibition by those drugs was assessed using a combination of the IC50 values and in vivo Cmax values from pharmacokinetic studies at their commercial doses and administration routes in the literature.. Fifteen bovine medicines or metabolites showed in vitro inhibition on one or more bovine hepatic CYP450 metabolisms with different IC50 values. Desfuroylceftiour (active metabolite of ceftiofur), nitroxinil and flunixin have the potential to inhibit one of the bovine hepatic CYP450 isoforms in vivo at their commercial doses and administration routes. The rest of the bovine medicines had low risks of in vivo bovine hepatic CYP450 inhibition.. This combination of in vitro assay and in vivo Cmax data provides a good approach to assess the inhibition of bovine medicines on bovine hepatic CYP450.

Topics: Animals; Cattle; Cephalosporins; Clonixin; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Inhibitory Concentration 50; Microsomes, Liver; Nitroxinil; Veterinary Drugs

Violative drug residues in animal-derived foods are a global food safety concern. The use of a fixed main metabolite to parent drug (M/D) ratio determined in healthy animals to establish drug tolerances and withdrawal times in diseased animals results in frequent residue violations in food-producing animals. We created a general physiologically based pharmacokinetic model for representative drugs (ceftiofur, enrofloxacin, flunixin, and sulfamethazine) in cattle and swine based on extensive published literature. Simulation results showed that the M/D ratio was not a fixed value, but a time-dependent range. Disease changed M/D ratios substantially and extended withdrawal times; these effects exhibited drug- and species-specificity. These results challenge the interpretation of violative residues based on the use of the M/D ratio to establish tolerances for metabolized drugs.

Topics: Animals; Calibration; Cattle; Cephalosporins; Clonixin; Drug Residues; Enrofloxacin; Fluoroquinolones; Food Contamination; Food Safety; Humans; Models, Theoretical; Species Specificity; Sulfamethazine; Swine; Veterinary Drugs

A simple, cow-side test for the presence of drug residues in live animal fluids would provide useful information for tissue drug residue avoidance programs. This work describes adaptation and evaluation of rapid screening tests to detect drug residues in serum and urine. Medicated heifers had urine, serum, and tissue biopsy samples taken while on drug treatment. Samples were tested by rapid methods and high-performance liquid chromatography (HPLC). The adapted microbial inhibition method, kidney inhibition swab test, was useful in detecting sulfadimethoxine in serum, and its response correlated with the prescribed withdrawal time for the drug, 5 to 6 days posttreatment. The lateral flow screening method for flunixin and beta-lactams, adapted for urine, was useful in predicting flunixin in liver detected by HPLC, 96 h posttreatment. The same adapted methods were not useful to detect ceftiofur in serum or urine due to a lack of sensitivity at the levels of interest. These antemortem screening test studies demonstrated that the method selected, and the sampling matrix chosen (urine or serum), will depend on the drug used and should be based on animal treatment history if available. The live animal tests demonstrated the potential for verification that an individual animal is free of drug residues before sale for human consumption.

Topics: Animals; Anti-Bacterial Agents; beta-Lactams; Cattle; Cephalosporins; Chromatography, High Pressure Liquid; Clonixin; Drug Residues; Female; Kidney; Liver

Three groups of five pigs were inoculated intratracheally with Escherichia coli lipopolysaccharides, and 24 hours later with 10 x 10(9) colony-forming units of a non-toxigenic strain of Pasteurella multocida type A; a fourth group was left uninoculated as controls. The three inoculated groups received either no treatment (positive controls), or were treated with 3 mg/kg ceftiofur intramuscularly once a day for five consecutive days, either alone or combined with 2 mg/kg flunixin intramuscularly once a day for three consecutive days. The sustained coughing and hyperthermia recorded in the positive controls disappeared after two days and three days of treatments, respectively, in the treated animals, and the reductions in daily weight gain and changes in breathing pattern observed in the controls were not observed in the treated animals. There were no significant differences between the pigs treated with ceftiofur alone or ceftiofur combined with flunixin. In the positive controls, the number of inflammatory cells in samples of bronchoalveolar lavage fluid continued to increase up to 15 days after inoculation, whereas in the treated animals there were similar increases at six days but the numbers had decreased to baseline levels after 15 days. Similarly, in the treated animals the volume of the lung lesions was significantly less than in the control animals, but the inclusion of flunixin in the treatment regimen had no significant additional effect.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Bronchopneumonia; Cephalosporins; Clonixin; Cough; Escherichia coli; Escherichia coli Infections; Female; Lipopolysaccharides; Male; Pasteurella Infections; Pasteurella multocida; Swine; Swine Diseases; Treatment Outcome

Neonatal camelids can develop hyperglycemia, hypernatremia, and hyperosmolarity in response to a combination of stress and inadequate water intake. Clinical signs of this syndrome include a fine head tremor, ataxia, and a base-wide stance of the hind limbs, but biochemical analyses are necessary to confirm the diagnosis. Camelids appear to be susceptible to this syndrome because of a poor insulin response to hyperglycemia; hypernatremia results from free water loss associated with glucose diuresis. Water loss associated with glucose diuresis may necessitate a higher rate of fluid administration in camelids with this syndrome than is typically used for treatment of hypernatremia in calves.

Topics: Animals; Animals, Newborn; Anorexia; Anti-Inflammatory Agents, Non-Steroidal; Body Temperature; Camelids, New World; Cephalosporins; Clonixin; Diuresis; Female; Hydrogen-Ion Concentration; Hyperglycemia; Hypernatremia; Isotonic Solutions; Osmolar Concentration; Penicillin G; Ringer's Solution; Sodium; Syndrome; Tachycardia

Medical management was unable to prevent the development of an extrapulmonary abscess in a 10-year-old Thoroughbred gelding with anaerobic pleuropneumonia. Intercostal thoracostomy achieved drainage of the abscess. Resolution of the abscess and subsequent bronchopleural fistulas was monitored by ultrasonography and video-endoscopy. The horse returned to training 4 mo after discharge.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antitrichomonal Agents; Cephalosporins; Chloramphenicol; Clonixin; Combined Modality Therapy; Drainage; Endoscopy; Enrofloxacin; Fluoroquinolones; Horse Diseases; Horses; Lung Abscess; Male; Metronidazole; Pleura; Pleuropneumonia; Quinolones; Therapeutic Irrigation; Thoracic Surgery; Thoracostomy; Trimethoprim; Ultrasonography