Absorption, Distribution and Excretion
A study of 4 male and 4 female Sprague-Dawley rats treated intramuscularly with (14)C-ceftiofur (2 mg/kg bw) revealed that 55% of the administered dose was excreted in the urine and about 30% in the GI tract and feces. The major urinary metabolite was desfuroylceftiofur (DFC). The metabolism of ceftiofur was similar in calves administered (14)C-ceftiofur (2 mg/kg bw) via the i.m. route. Unmetabolized ceftiofur was also present in the urine (4.4-21% of total radioactivity).
A group of Sprague-Dawley rats (7/sex) received single oral doses of (14)C-ceftiofur (200 mg/kg bw) in a comparative study with calves. Approximately 55% of the total dose was recovered in the urine and the rest was present in the feces and GI tract. Plasma concentration at 6 hr was 1 mg/kg and trace amounts of ceftiofur were present in all tissues (i.e. liver, muscle and fat). The highest residue levels (0.7 mg/kg) were present in kidney.
A study of lactating cows treated with (14)C-ceftiofur (2.3 mg/kg bw/day for 5 days) revealed that 32-38% of the radioactivity was present in the milk as free metabolites. The major metabolite was desfuroylceftiofur cysteine disulfide representing 7-9% of the total radioactivity. No parent compound was detected in the milk.
A study of im administration of (14)C-ceftiofur in a bull revealed that 55% of the administered dose was excreted in the urine and approximately 30% in the GI tract and feces. The initial metabolite in both urine and plasma was desfuroylceftiofur. HPLC analysis of radioactive metabolites was similar to the results found in the rat studies. A number of metabolites were produced, the major metabolite (87% of total urinary metabolites) being desfuroylceftiofur acetamide conjugates. No parent compound was observed in the urine.
For more Absorption, Distribution and Excretion (Complete) data for CEFTIOFUR (13 total), please visit the HSDB record page.

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Metabolism / Metabolites
A study of 4 male and 4 female Sprague-Dawley rats treated intramuscularly with (14)C-ceftiofur (2 mg/kg bw) revealed that 55% of the administered dose was excreted in the urine and about 30% in the GI tract and faeces. The major urinary metabolite was desfuroylceftiofur (DFC). The metabolism of ceftiofur was similar in calves administered (14)C-ceftiofur (2 mg/kg bw) via the i.m. route. Unmetabolized ceftiofur was also present in the urine (4.4-21% of total radioactivity).
A group of Sprague-Dawley rats (7/sex) received single oral doses of (14)C-ceftiofur (200 mg/kg bw) in a comparative study with calves. Approximately 55% of the total dose was recovered in the urine and the rest was present in the feces and GI tract. ... The major urinary metabolite was ceftiofursulfoxide cysteine thioester.
HPLC analysis of metabolites of (14)C-ceftiofur formed by arochlor-induced rat liver S-9 fractions in vitro revealed that desfuroylceftiofur was the major metabolite. Low doses (119 mg/kg bw) of ceftiofur were completely metabolized within 15 minutes. Higher doses (857 mg/kg bw) were converted to desfuroylceftiofur after 60 minutes of incubation.
A study in 8-week old Sprague-Dawley rats (7/sex) treated with (14)C-ceftiofur (800 mg/kg bw/day) by oral gavage for 5 days revealed several urinary metabolites, including desfuroylceftiofur, ceftiofur sulfoxide, and cysteine disulfide.
For more Metabolism/Metabolites (Complete) data for CEFTIOFUR (15 total), please visit the HSDB record page.

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Biological Half-Life
Six Friesian calves (3/sex) were treated with ceftiofur according to different protocols including one single im and iv injection at 1 mg/kg bw, and 5 i.m. injections at 1 mg/kg bw at 24 hr intervals. ... The half life (0.07 hr) was short due to rapid metabolism to desfuroylceftiofur. The t1/2 of desfuroylceftiofur after im and iv administration were similar (9.7 and 8.6 hr, respectively).
A study of 4 calves (sex and breed unspecified) administered ceftiofur intramuscularly daily for 4 days at 2 dose levels (2.2 or 4.4 mg/kg bw/day) demonstrated a plasma half life of 3.5 hr. ... Plasma half life of the metabolite desfuroylceftiofur was 9.7 h after im administration.
A study of 4- to 5-month old Yorkshire-Hampshire pigs (6/sex) treated with 3 daily im injections of (14)C-ceftiofur (5.2 mg/kg bw) produced similar results to those observed in rats and cattle. ... The half life of desfuroylceftiofur was 13.5 hr after im treatment and 12.2 hr after iv treatment. /Desfuroylceftiofur/

Ceftiofur is a third generation cephalosporin antibiotic, first described in 1987, and now used in veterinary medicine. It is marketed by pharmaceutical company Zoetis as Excenel, and is the active ingredient in that company's Specramast LC (lactating cow formula) product. It is resistant to hydrolysis by beta-lactamase, and has activity against both Gram-positive and Gram-negative bacteria. E. coli strains resistant to ceftiofur have been reported. The metabolite desfurolyceftiofur also has antibiotic activity, consequently the two compounds are measured together to monitor for antibiotic activity in the milk.
Ceftiofur is a semisynthetic, beta-lactamase-stable, broad-spectrum, third-generation cephalosporin with antibacterial activity. Ceftiofur binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.
See also: Ceftiofur Sodium (active moiety of); Ceftiofur Hydrochloride (has salt form); Ceftiofur Crystalline Free Acid (annotation moved to).

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Drug Indication
PigsTreatment of bacterial respiratory disease associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis and Streptococcus suis. Treatment of septicaemia, polyarthritis or polyserositis associated with Streptococcus suis infection. CattleTreatment of acute interdigital necrobacillosis in cattle also known as Panaritium or foot rot. Treatment of acute post-partum (puerperal) metritis in cattle, in cases where treatment with another antimicrobial has failed.

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Mechanism of Action
Ceftiofur sodium is a third generation broad-spectrum cephalosporin, formulated as an intramuscular injection, which is used to treat respiratory diseases in swine, ruminants and horses. The thioester bond on ceftiofur is rapidly cleaved to give desfuroylceftiofur which is further metabolized to a disulfide dimer and various desfuroylceftiofur-protein and amino acid conjugates.
Cephalosporins ... bind to penicillin-binding proteins located beneath the cell wall and thereby interfere with the action of transpeptidase and other cell-wall enzymes. A residual antibacterial effect is also evident with the cephalosporins. /Cephalosporins/

C19H17N5O7S3

523.55

523.028

80370-57-6

Ceftiofur hydrochloride;103980-44-5;Ceftiofur sodium;104010-37-9

6328657

White to off-white solid powder

1.8±0.1 g/cm3

1.820

2.05

3

13

9

34

945

2

C(C1=C(CSC(C2OC=CC=2)=O)CS[C@@H]2[C@@H](C(N12)=O)NC(=O)/C(/C1N=C(N)SC=1)=N\OC)(=O)O

ZBHXIWJRIFEVQY-IHMPYVIRSA-N

InChI=1S/C19H17N5O7S3/c1-30-23-11(9-7-34-19(20)21-9)14(25)22-12-15(26)24-13(17(27)28)8(5-32-16(12)24)6-33-18(29)10-3-2-4-31-10/h2-4,7,12,16H,5-6H2,1H3,(H2,20,21)(H,22,25)(H,27,28)/b23-11-/t12-,16-/m1/s1

(6R,7R)-7-[[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-(furan-2-carbonylsulfanylmethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: This product requires protection from light (avoid light exposure) during transportation and storage.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~191.00 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (4.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)