Absorption, Distribution and Excretion
A study of four male and four female Sprague-Dawley rats showed that after intramuscular injection of (14)C-cefotiofur (2 mg/kg body weight), 55% of the administered dose was excreted in the urine, and approximately 30% was excreted in the gastrointestinal tract and feces. The major urinary metabolite was desfuranylcefotiofur (DFC). Ceftiofur metabolism in calves after intramuscular injection of (14)C-cefotiofur (2 mg/kg body weight) was similar to that in rats. Unmetabolized ceftiofur was also present in the urine (accounting for 4.4–21% of total radioactivity). In a comparative study with calves, a group of Sprague-Dawley rats (7 males and 7 females) were given a single oral dose of (14)C-cefotiofur (200 mg/kg body weight). Approximately 55% of the total dose was excreted in the urine, with the remainder present in the feces and gastrointestinal tract. The 6-hour plasma concentration was 1 mg/kg, and trace amounts of ceftiofur were present in all tissues, including the liver, muscle, and fat. The highest residual amount was found in the kidneys (0.7 mg/kg). A study of lactating cows treated with 14C-cefotiofur (2.3 mg/kg body weight/day for 5 consecutive days) showed that 32-38% of the radioactivity was present in the milk as free metabolites. The major metabolite was desfurylcefotiofur cysteine disulfide, accounting for 7-9% of the total radioactivity. The parent compound was not detected in the milk. A study of bulls administered intramuscular (14)C-cefotiofur showed that 55% of the administered dose was excreted in the urine, and approximately 30% was excreted in the gastrointestinal tract and feces. The initial metabolite in the urine and plasma was desfurylcefotiofur. HPLC analysis of the radioactive metabolites yielded results similar to those in rat studies. Multiple metabolites were produced, with the major metabolite (accounting for 87% of total urinary metabolites) being desfurylceftiofur acetamide conjugate. The parent compound was not detected in the urine. For more complete data on the absorption, distribution, and excretion of ceftiofur (13 in total), please visit the HSDB record page. Metabolites/Metabolites A study of four male and four female Sprague-Dawley rats showed that after intramuscular injection of (14)C-ceftiofur (2 mg/kg body weight), 55% of the administered dose was excreted in the urine, and approximately 30% was excreted in the gastrointestinal tract and feces. The major urinary metabolite was desfurylceftiofur (DFC). Similar metabolism of ceftiofur was observed in calves after intramuscular injection of (14)C-ceftiofur (2 mg/kg body weight). Unmetabolized ceftiofur was also present in the urine (accounting for 4.4–21% of total radioactivity). In a comparative study with calves, a group of Sprague-Dawley rats (7 males and 7 females) were given a single oral dose of (14)C-cefotiofur (200 mg/kg body weight). Approximately 55% of the total dose was recovered in the urine, with the remainder present in the feces and gastrointestinal tract. …The major urinary metabolite was ceftiofur sulfoxide cysteine thioester. High-performance liquid chromatography analysis of (14)C-cefotiofur metabolites produced in the S-9 fraction of rat liver induced by arochlor in vitro showed that desfuranylcefotiofur was the major metabolite. Low doses (119 mg/kg body weight) of ceftiofur were completely metabolized within 15 minutes. Higher doses (857 mg/kg body weight) were converted to desfuranylcefotiofur after 60 minutes of incubation.
A study of 8-week-old Sprague-Dawley rats (7 males and 7 females) showed that after 5 consecutive days of oral administration of (14)C-cefotiofur (800 mg/kg body weight/day), multiple metabolites, including desfurylcefotiofur, ceftiofur sulfoxide, and cysteine disulfide, were detected in the urine.
More complete data on the metabolites/metabolites of ceftiofur (15 in total) can be found on the HSDB record page.

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Biological half-life
Six Friesian calves (3 males and 3 females) were treated with ceftiofur according to different regimens, including a single intramuscular and intravenous injection (1 mg/kg body weight) and 5 intramuscular injections (1 mg/kg body weight). Dosing was performed every 24 hours. …The half-life (0.07 hours) is short due to its rapid metabolism to desfurylcefotiofur. The half-lives of desfuryl ceftiofur were similar after intramuscular and intravenous administration (9.7 hours and 8.6 hours, respectively). A study of four calves (sex and breed not specified) showed a plasma half-life of 3.5 hours after daily intramuscular administration of ceftiofur at doses of 2.2 or 4.4 mg/kg body weight/day for four consecutive days. … The plasma half-life of the metabolite desfuryl ceftiofur after intramuscular administration was 9.7 hours. A study of four- to five-month-old Yorkshire-Hampshire pigs (six of each sex) receiving daily intramuscular administration of (14)C-cefotiofur (5.2 mg/kg body weight) for three consecutive days yielded results similar to those observed in rats and cattle. The half-life of desfuryl ceftiofur after intramuscular administration was 13.5 hours, compared to 12.2 hours after intravenous administration.

Ceftiofur is a third-generation cephalosporin antibiotic, first discovered in 1987 and now used in veterinary medicine. It is marketed by Zoetis under the brand name Excenel and is the active ingredient in their Speramast LC (lactating cow formula) product. Ceftiofur is resistant to hydrolysis by β-lactamases and has antibacterial activity against both Gram-positive and Gram-negative bacteria. Ceftiofur-resistant Escherichia coli strains have been reported. Its metabolite, desfuran ceftiofur, also has antibacterial activity; therefore, both compounds are often tested simultaneously to monitor antibacterial activity in milk. Ceftiofur is a semi-synthetic, β-lactamase-stable, broad-spectrum third-generation cephalosporin antibiotic with antibacterial activity. Ceftiofur binds to and inactivates penicillin-binding protein (PBP) located on the inner membrane of bacterial cell walls. PBP is an enzyme involved in the late stages of bacterial cell wall assembly and cell wall remodeling during growth and division. Inactivation of PBP interferes with the cross-linking of peptidoglycan chains, which is crucial for maintaining the strength and rigidity of bacterial cell walls. This leads to weakening of the bacterial cell wall and ultimately cell lysis.
See also: Ceftiofur sodium (active ingredient); Ceftiofur hydrochloride (salt form); Ceftiofur crystals free acid (note moved to).
Indications

Swine: Treatment of bacterial respiratory diseases caused by Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Streptococcus suis.
For the treatment of septicemia, polyarthritis, or polyserositis caused by Streptococcus suis infection. For the treatment of acute interdigital necrotizing bacillus infection in bovine plants (also known as Panalitium disease or hoof rot). For the treatment of acute postpartum (puerperal) metritis in bovine plants, especially when other antimicrobial treatments are ineffective.

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Mechanism of Action
Ceftiofur sodium is a third-generation broad-spectrum cephalosporin administered intramuscularly for the treatment of respiratory diseases in pigs, ruminants, and horses. The thioester bonds on ceftiofur rapidly cleave to form desfurylcetiofur, which is further metabolized into disulfide dimers and various desfurylcetiofur-protein and amino acid conjugates.
Cephalosporins…bind to penicillin-binding proteins located beneath the cell wall, thereby interfering with the activity of transpeptidase and other cell wall enzymes. Cephalosporins also exhibit some residual antibacterial activity. /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.)