Ceftiofur

HCID 6328657CAS 80370-57-6

Grundinformationen

Standard-SMILES
CO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)O)=C(CSC(=O)c3ccco3)CS[C@H]12)c1csc(N)n1
InChIKey
ZBHXIWJRIFEVQY-IHMPYVIRSA-N
Summenformel
C19H17N5O7S3
Durchschnittliche Molmasse
523,6 g/mol
Monoisotopische Masse
523,02901088

Überblick

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.

Namen und Bezeichner

Bevorzugter Name
Ceftiofur
IUPAC
(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

Namen und Synonyme

Ceftiofur80370-57-6NaxcelCeftiofurumCeftiofur crystalline free acidDTXSID704670283JL932I1CDTXCID5026702Excede(6R,7R)-7-[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetamido]-3-[(furan-2-carbonylsulfanyl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid5-Thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7-(((2Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl)amino)-3-(((2-furanylcarbonyl)thio)methyl)-8-oxo-, (6R,7R)-Ceftiofur Free Acid
Weitere Namen anzeigen
Excede Sterile(6R,7R)-7-((2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetamido)-3-((furan-2-carbonylsulfanyl)methyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acidEXCEDE FOR SWINERefChem:54736Excede for Swine SterileCeftiofur (INN)CEFTIOFUR [INN](6R,7R)-7-(2-(2-Amino-4-thiazolyl)glyoxylamido)-3-(mercaptomethyl)-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-ene-2-carboxylic acid, 7(sup 2)-(Z)-(O-methyloxime), 2-furoate (ester)

Datenbank-Bezeichner

CAS
80370-57-6
PubChem CID
6328657
DTXSID
DTXSID7046702
ChEMBL
CHEMBL222913
UNII
83JL932I1C
EC Number
688-302-4
Nikkaji
J33.126K

Eigenschaften

Berechnete Struktureigenschaften

XLogP
0,2
Polarare Oberfläche (TPSA)
256 Ų
H-Brücken-Donoren
3
H-Brücken-Akzeptoren
13
Frei drehbare Bindungen
9
Schwere Atome
34

Experimentelle und physikochemische Eigenschaften

DrugsPharmaceuticals -> Antibiotics
Animal Drugs · 4 Einträge

EMA approved medicines: Veterinary medicine

Active Ingredients (Ceftiofur Crystalline Free Acid) -> FDA Greenbook

Pharmaceuticals -> UK Veterinary Medicines Directorate List

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

Other Experimental Properties · 2 Einträge

Mol wt: 545.55 /Monosodium salt/

Mol wt: 560.03 /Monohydrochloride/

Sicherheit und Regulatorisches

GHS-Klassifizierung

GHS Classification · 5 Einträge

This chemical does not meet GHS hazard criteria for 66.7% (2 of 3) of all reports.

Danger

H317 (33.3%): May cause an allergic skin reaction [Warning Sensitization, Skin]

P233, P260, P261, P271, P272, P280, P284, P302+P352, P304+P340, P321, P333+P317, P342+P316, P362+P364, P403, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 3 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Gefahrenhinweise

Regulatory InformationCeftiofur: Does not have an individual approval but may be used under an appropriate group standard
FDA Requirements · 5 Einträge

Implantation or injectable dosage form new animal drugs. Ceftiofur crystalline free acid. ... (1) Swine. Indications for use: For the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Streptococcus suis. ... (2) Cattle. Indications for use. For the treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni in beef, non-lactating dairy, and lactating dairy cattle. For the control of respiratory disease in beef and non-lactating dairy cattle which are at high risk of developing BRD associated with M. haemolytica, P. multocida, and H. somni. /Ceftiofur crystalline free acid/

Implantation or injectable dosage form new animal drugs. Ceftiofur hydrochloride. ... (1) Swine. Indications for use: For treatment and control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis. ... (2) Cattle. Indications for use: For treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia haemolytica, P. multocida, and Histophilus somni; acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus; and acute metritis (0 to 14 days post-partum) associated with bacteria susceptible to ceftiofur. /Ceftiofur hydrochloride/

Implantation or injectable dosage form new animal drugs. Ceftiofur sodium. ... (1) Swine. Indications for use: For treatment and control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis. ... (2) Cattle. Indications for use: For treatment of bovine respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica, P. multocida, and Histophilus somni in beef and dairy cattle; and for treatment of acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus. ... (3) Sheep. Indications for use: For treatment of sheep respiratory disease (pneumonia) associated with M. haemolytica and P. multocida. ... (4) Goats. Indications for use: For treatment of caprine respiratory disease (goat pneumonia) associated with M. haemolytica and P. multocida. ... (5) Chickens. Indications for use: For control of early mortality associated with Escherichia coli organisms susceptible to ceftiofur in day-old chicks. ... (6) Turkeys. Indications for use: For control of early mortality associated with E. coli organisms susceptible to ceftiofur in day-old poults. ... (7) Horses. Indications for use: For treatment of respiratory infections in horses associated with Streptococcus zooepidemicus. ... (8) Dogs. Indications for use: For treatment of canine urinary tract infections associated with E. coli and Proteus mirabilis. /Ceftiofur sodium/

Intramammary dosage forms. Ceftiofur. ... (1) Lactating cows. Indications for use. For the treatment of clinical mastitis in lactating dairy cattle associated with coagulase-negative staphylococci, Streptococcus dysgalactiae, and Escherichia coli. ... (2) Dry cows. For the treatment of subclinical mastitis in dairy cattle at the time of dry off associated with Staphylococcus aureus, Streptococcus dysgalactiae, and Streptococcus uberis.

For more FDA Requirements (Complete) data for CEFTIOFUR (6 total), please visit the HSDB record page.

Hazard Classes and CategoriesSkin Sens. 1 (33.3%)

Sicherheit und Schutzausrüstung

Storage Conditions · 2 Einträge

Store unreconstituted product at controlled room temperature, 20 to 25 °C (68 to 77 °F), unless otherwise specified by manufacturer. Store reconstituted product either in a refrigerator at 2 to 8 °C (36 to 46 °F) for up to seven days or at controlled room temperature, 20 to 25 °C (68 to 77 °F), for up to twelve hours, unless otherwise specified by manufacturer. Protect from light. /Ceftiofur sodium for injection/

Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing. /Ceftiofur hydrochloride injection/

Disposal Methods · 1 Eintrag

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Allowable Tolerances · 1 Eintrag

Tolerances-(1) Poultry, and sheep. A tolerance for residues of ceftiofur in edible tissue is not required. (2) Swine. The tolerances for desfuroylceftiofur (marker residue) are: (i) Kidney (target tissue). 0.25 parts per million (ppm). (ii)Liver. 3 ppm. (iii) Muscle. 2 ppm. (3) Cattle. The tolerances for desfuroylceftiofur (marker residue) are: (i) Kidney (target tissue). 0.4 ppm. (ii) Liver. 2 ppm. (iii)Muscle. 1 ppm. (iv) Milk. 0.1 ppm.

Toxikologische Informationen

Environmental Fate · 3 Einträge

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 3,700(SRC), determined from a structure estimation method(2), indicates that ceftiofur is expected to have slight mobility in soil(SRC). An estimated pKa of 3.7 (carboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(3), indicates that this compound will exist primarily as an anion in the environment and anions generally have higher mobility in soils than their neutral counterparts(4). Volatilization of ceftiofur from moist soil surfaces is not expected to be an important fate process(SRC) since anions do not volatilize. Ceftiofur is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6X10-20 mm Hg(SRC), determined from a fragment constant method(6). Half-lives reported for the aerobic biodegradation of cefiofur sodium in clay loam at pH 5, sand at pH 7, and silty clay loam at pH 9 were 22.2, 49, and 41.1 days, respectively(7-9).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 3,700(SRC), determined from a structure estimation method(2), indicates that ceftiofur is expected to adsorb to suspended solids and sediment(SRC). However, an estimated pKa of 3.7 (carboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(3), indicates that this compound will exist primarily as an anion in the environment, and anions do not adsorb to sediment as strongly as their neutral counterparts(4). Volatilization from water surfaces is not expected because anions do not volatilize. According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of 1.6(6) and a regression-derived equation(7), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Half-lives reported for the aqueous hydrolysis of ceftiofur sodium were 22.2 days at pH 5, 49 days at pH 7, and 41.1 days at pH 9(8,9). Half-lives reported for the aerobic biodegradation of ceftiofur sodium in clay loam at pH 5, sand at pH 7, and silty clay loam at pH 9 were 22.2, 49, and 41.1 days, respectively(8-10).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), ceftiofur, which has an estimated vapor pressure of 6X10-20 mm Hg(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase ceftiofur may be removed from the air by wet or dry deposition(SRC). Ceftiofur contains chromophores that absorb at wavelengths >290 nm indicating that this substance may be susceptible to direct photolysis by sunlight(3); however photodegradation of ceftiofur sodium has been reported to be minimal(4).

Soil Adsorption/Mobility · 1 Eintrag

Using a structure estimation method based on molecular connectivity indices(1), the Koc of ceftiofur can be estimated to be 3,700(SRC). According to a classification scheme(2), this estimated Koc value suggests that ceftiofur is expected to have slight mobility in soil. However, an estimated pKa of 3.7 (carboxylic acid)(SRC), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(3), indicates that this compound will exist primarily as an anion in the environment and anions generally have higher mobility in soils than their neutral counterparts(4).

Artificial Pollution SourcesCeftiofur's production and use as a veterinary antibacterial medicine(1,2) may result in its release to the environment through various waste streams(SRC).
Environmental BiodegradationAEROBIC: Half-lives reported for the aerobic biodegradation of cefiofur sodium in clay loam at pH 5, sand at pH 7, and silty clay loam at pH 9 were 22.2, 49, and 41.1 days, respectively(1-3).
Environmental Bioconcentration · 1 Eintrag

An estimated BCF of 3 was calculated for ceftiofur(SRC), using an estimated log Kow of 1.6(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Volatilization from Water/Soil · 1 Eintrag

An estimated pKa of 3.7 (carboxylic acid)(1), calculated using a method based on linear free energy relationships and perturbed molecular orbital theory(2), indicates that this compound will exist primarily as an anion in the environment. Volatilization from moist soil or water surfaces is not expected(SRC) since anions do not volatilize. Ceftiofur is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 6X10-20 mm Hg(SRC), determined from a fragment constant method(3).

Regulatorische Informationen

FDA Requirements · 5 Einträge

Implantation or injectable dosage form new animal drugs. Ceftiofur crystalline free acid. ... (1) Swine. Indications for use: For the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Streptococcus suis. ... (2) Cattle. Indications for use. For the treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni in beef, non-lactating dairy, and lactating dairy cattle. For the control of respiratory disease in beef and non-lactating dairy cattle which are at high risk of developing BRD associated with M. haemolytica, P. multocida, and H. somni. /Ceftiofur crystalline free acid/

Implantation or injectable dosage form new animal drugs. Ceftiofur hydrochloride. ... (1) Swine. Indications for use: For treatment and control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis. ... (2) Cattle. Indications for use: For treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia haemolytica, P. multocida, and Histophilus somni; acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus; and acute metritis (0 to 14 days post-partum) associated with bacteria susceptible to ceftiofur. /Ceftiofur hydrochloride/

Implantation or injectable dosage form new animal drugs. Ceftiofur sodium. ... (1) Swine. Indications for use: For treatment and control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis. ... (2) Cattle. Indications for use: For treatment of bovine respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica, P. multocida, and Histophilus somni in beef and dairy cattle; and for treatment of acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus. ... (3) Sheep. Indications for use: For treatment of sheep respiratory disease (pneumonia) associated with M. haemolytica and P. multocida. ... (4) Goats. Indications for use: For treatment of caprine respiratory disease (goat pneumonia) associated with M. haemolytica and P. multocida. ... (5) Chickens. Indications for use: For control of early mortality associated with Escherichia coli organisms susceptible to ceftiofur in day-old chicks. ... (6) Turkeys. Indications for use: For control of early mortality associated with E. coli organisms susceptible to ceftiofur in day-old poults. ... (7) Horses. Indications for use: For treatment of respiratory infections in horses associated with Streptococcus zooepidemicus. ... (8) Dogs. Indications for use: For treatment of canine urinary tract infections associated with E. coli and Proteus mirabilis. /Ceftiofur sodium/

Intramammary dosage forms. Ceftiofur. ... (1) Lactating cows. Indications for use. For the treatment of clinical mastitis in lactating dairy cattle associated with coagulase-negative staphylococci, Streptococcus dysgalactiae, and Escherichia coli. ... (2) Dry cows. For the treatment of subclinical mastitis in dairy cattle at the time of dry off associated with Staphylococcus aureus, Streptococcus dysgalactiae, and Streptococcus uberis.

For more FDA Requirements (Complete) data for CEFTIOFUR (6 total), please visit the HSDB record page.

Chemie und Industrie

Pharmakologische Informationen

ATC Code · 2 Einträge

QJ - Antiinfectives for systemic use

QJ - Antiinfectives for systemic use

Mechanism of Action · 2 Einträge

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/

Biological Half-Life · 3 Einträge

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/

Metabolism/Metabolites · 5 Einträge

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.

MeSH Pharmacological ClassificationSubstances that inhibit the growth or reproduction of BACTERIA.
Absorption, Distribution and Excretion · 5 Einträge

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.

Verwendung und Herstellung

Uses · 2 Einträge

Vet: Antibacterial ... moderatley active against gram-positive bacteria ... are active against gram-negative bacteria ... highly resistant to beta-lactamase enzymes /Third-generation cephalosporins/

Mesh Heading: anti-bacterial agents

Methods of Manufacturing... B. Labeeuw, A. Salhi, European patent 36812; ... US patent 4464367 (1981, 1984 both to Sanofi).
Formulations/Preparations · 2 Einträge

Veterinary-labeled product(s): 50 mg per mL (Rx) (Naxcel). /Ceftiofur sodium for injection/

Veterinary-labeled product(s): 50 mg per mL (Rx) (Excenel RTU). /Ceftiofur hydrochloride injection/

Use Classification · 3 Einträge

Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients

Veterinary Drug -> ANTIMICROBIAL_AGENT -> JECFA Functional Classes

Pharmaceuticals -> Animal Drugs -> Approved in Taiwan

General Manufacturing Information... approved for use in cows and dogs

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