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Cefepime

Brand Name(s) in US
Cefepime
Cefepime structure
CAS No.
88040-23-7
Chemical Name:
Cefepime
Synonyms
CFPM;Cefpim;CEFEPIME;FR 81335;Tsefepim;BMY 28142;Cefepime Jp;Cefepime, >98%;Cefepime sodium;Cefepime (CFPM)
CBNumber:
CB1737417
Molecular Formula:
C19H24N6O5S2
Formula Weight:
480.56
MOL File:
88040-23-7.mol

Cefepime Properties

Melting point:
150 C
CAS DataBase Reference
88040-23-7(CAS DataBase Reference)
FDA UNII
807PW4VQE3
NCI Dictionary of Cancer Terms
cefepime
ATC code
J01DE01
SAFETY
  • Risk and Safety Statements
Hazard Codes  Xi
Risk Statements  36/37/38-42/43
Safety Statements  22-26-36/37/39
HS Code  29419000

Cefepime Chemical Properties,Uses,Production

Brand Name(s) in US

Maxipime

Description

Cefepime is a new fourth-generation parenteral cephalosporine antibiotic launched in 1993 in Sweden and France. Cefepime has broad spectrum antimicrobial activity against Staphylococcus, Strepfococcus, Pseudomonas, and the Enterobacteriaceae, including many bacterial isolates that are resistant to commonly used ceftazidime and cefotaxime. Its efficacy has been demonstrated in the treatment of lower respiratory tract infections especially pneumonia, intra-abdominal and urinary tract infections, skin and soft tissue infections, chronic osteomyelitis and in prophylaxis of biliary tract and prostate infections. It is well tolerated by patients and is reported to exhibit no significant drug interactions.

Chemical Properties

colorless Powder

Originator

Bristol-Myers Squibb (U.S.A.)

Uses

Cefepime is used for bacterial infections caused by microorganisms that are sensitive to drugs in septicemia, bacteriemia, complicated infections of the upper and lower sections of the urinary system, pneumonia, pulmonary abscesses, emphysema of the pleura, fever in patients with neutropenia, and infected skin and soft tissue wounds. Synonyms of this drug are maxipime, cepim, cepimex, and others.

Manufacturing Process

A mixture of ethyl (Z)-2-hydroxyimino-2-(2-tritylaminothiazol-4-yl) acetate (5 g, 10.9 mmoles), methyliodide (2.04 ml, 32.8 mmoles) and K2CO3 (4.54 g, 32.8 mmoles) in dry DMSO (100 ml) was stirred at room temperature overnight and then poured into water (250 ml). The precipitate was collected, washed with water and dried to give 2-methoxyimino-2-(2-tritylaminothiazol- 4-yl) acetate (1.15 g, melting point 115°C (dec.))
Ethyl (Z)-2-hydroxyimino-2-(2-tritylaminothiazol-4-yl) acetate (6 g, 12.7 mmol) in ethanol was treated with 2 N NaOH (12.7 ml) at room temperature overnight. The mixture was adjusted to pH 8 by the addition of powdered dry ice and the solvent evaporated. The residue was dissolved in water (100 ml) and was added to the solution which was acidified with 1 N HCl to pH 2 and then extracted with ethyl acetate. Extract was evaporated, the residue was crystallized from ethyl acetate-hexane to afford ethyl (Z)-2-hydroxyimino-2- (2-tritylaminothiazol-4-yl)acetic acid (5.56 g, melting point 138-143°C (dec.)).
To a suspension of phosphate buffer (pH 7, 162.5 ml) and wheat bran (20 g, dry) at room temperature was added 7-phenylacetimidocephalosporanic acid sodium salt (5 g). After 5 hours the suspension was filtered to remove wheat bran and the filtrate was cooled to 5-10°C, then was added methylene chloride (32 ml) and 0.5 M solution of diphenyldiazomethane in methylene chloride (24 ml). The pH was then adjusted to 3.0 with 28% phosphoric acid. After 1 hour the mixture was allowed to rise to 20°C. Heptane was slowly added (56 ml) and was recovered benzhydryl 3-hydroxymethyl-7- phenylacetamido-3-cephem-4-carboxylate (3.0 g, 50%).
The mixture of PCl5(8.3 g) and pyridine (3.2 g) in CH2Cl2 was added to benzhydryl 3-hydroxymethyl-7-phenylacetamido-3-cephem-4-carboxylate (5.1 g) at -40°C. The mixture was stirred at -10°C for 15 minutes and allowed to stand at -15-10°C for 7 hours. To the solution at -20°C was added propane- 1,3-diol (10 ml) and the mixture was allowed to stand at -20°C for 16 hours and then at room temperature for 20 minutes. The resulting solution was washed with ice-water and saturated aqueous NaCl (10 ml), dried and concentrated. The gummy residue (12 g) was dissolved in CHCl3-hexane (2:1), and subjected to chromatography using silica gel column and the same solvent as eluant. After evaporation of the solvents was obtained benzhydryl- 7-amino-3-chloromethyl-3-cephem-4-carboxylate (2.1 g, 51%, melting point >110°C(dec.)).
Benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate (2.29 g) was treated with bis(trimethylsilyl)acetamide (4.06 ml) at room temperature for 50 min to give a clear solution. Top the solution was added an acid chloride solution, which was prepared from (Z)-2-hydroxyimino-2-(2- tritylaminothiazol-4-yl)acetic acid (2.04 g) and PCl5 (1.15 g) in methylene chloride (20 ml). The mixture was stirred at room temperature for 30 min, poured in cold water (200 ml) and extracted with ethyl acetate (100 ml x 3). After evaporation of the solution was obtained the syrup (4 g) which was chromatographed on a silica gel column by eluting with 10:1 and 3:1 mixture of toluene and ethyl acetate successively. After evaporation of the solvents was obtained benzhydryl 3-chloromethyl-7-[(Z)-2-methoxyimino-2-(2- tritylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate (2.62 g, 68%).
A mixture of the benzhydryl 3-chloromethyl-7-[(Z)-2-methoxyimino-2-(2- tritylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate (1.50 g, 1.79 mmoles) and NaI (1.34 g, 8.93 mmoles) in methyl ethyl ketone (30 ml) was stirred at room temperature for 1 hour. After evaporation of the solvent the residue was dissolved in ethyl acetate (100 ml) and washed with water, aqueous Na2S2O3 and aqueous NaCl, dried and evaporated to give 7-[(Z)-2- ethoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-iodomethyl-3-cephem- 4-carboxilate (1.47 g, 89%) as an amorphous powder.
A mixture of 7-[(Z)-2-ethoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3- iodomethyl-3-cephem-4-carboxilate (4.5 g, 4.83 mmoles) and N-methylpyrrolidine (0.65 ml, 6.28 mmoles) in CH2Cl2 (45 ml) was stirred at room temperature for 20 min. Ether (300 ml) was added to the mixture to separate the quaternary salt of the blocked cephalosporin, which was collected by filtration and treated with 90% trifluoroacetic acid (TFA) (40 ml) at room temperature for 1 hour. The mixture was then evaporated under reduced pressure below 20°C. The residue was triturated with ether to give the TFA salt of 7-[(Z)-2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-[(1- methyl-1-pyrrolidinium)methyl]-3-cephem-4-carboxylate (2.40 g), which was dissolved in methanol (5 ml) and treated with 1 M solution of sodium-2- ethylhexoate in ethyl acetate (8 ml) at room temperature for 30 min. After the addition of ethyl acetate (100 ml), the precipitate (1.94 g) formed was collected by filtration. HPLC analysis showed that the crude product was 7% pure with a 1:8 ratio of the δ3 isomer to the δ2 isomer. Purification of the product by HPLC was repeated three times (Lichrosorb RP-18, eluted with 5% aqueous methanol or 0.01 M ammonium phosphate buffer (pH 7.2 containing 5% of methanol) to give 35 mg (1.5%) of the title product as a colorless powder of 7-[(Z)-2-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]-3-[(1- methyl-1-pyrrolidinium)methyl]-3-cephem-4-carboxylate. Estimated purity (by HPLC) 90%. M.p. 150°C (dec.).

brand name

Maxipime; Axepim

Therapeutic Function

Antibiotic

Antimicrobial activity

Its activity against common pathogens is comparable to that of group 4 cephalosporins, but it is somewhat more active against Ps. aeruginosa. Like cefpirome it has low affinity for the molecular class C cephalosporinases of many Gram-negative rods and is consequently active against most strains of Citrobacter spp., Enterobacter spp., Serratia spp. and Ps. aeruginosa that are resistant to cefotaxime and ceftazidime. It has poor activity against L. monocytogenes and against anaerobic organisms.

Pharmacokinetics

Cmax 2 g intravenous (30-min infusion): c. 160 mg/L end infusion
Plasma half-life: c. 2 h
Volume of distribution: 14–20 L
Plasma protein binding: 10–19%
It is well distributed. Penetration into tissues, including lung, appears to be similar to that of other aminothiazoyl cephalosporins. Very low concentrations are achieved in CSF in the absence of meningeal inflammation. It is secreted in breast milk.
It is partially metabolized, but 85% of the dose is excreted unchanged in the urine, achieving a concentration approaching 1 g/L within 4 h of a 1 g intravenous dose. Dosage adjustment is required in patients with impaired renal function, but hepatic impairment does not affect the pharmacokinetic properties.

Clinical Use

Cefepime (Maxipime, Axepin) is a parenteral, β-lactamase–resistant cephalosporin that is chemically and microbiologicallysimilar to cefpirome. It also has a broadantibacterial spectrum, with significant activity against bothGram-positive and Gram-negative bacteria, including streptococci,staphylococci, Pseudomonas spp., and theEnterobacteriaceae. It is active against some bacterial isolatesthat are resistant to ceftazidime. The efficacy of cefepimehas been demonstrated in the treatment of urinary tract infections,lower respiratory tract infections, skin and soft tissueinfections, chronic osteomyelitis, and intra-abdominal andbiliary infections. It is excreted in the urine with a half-life of2.1 hours. It is bound minimally to plasma proteins. Cefepimeis also a fourth-generation cephalosporin.

Clinical Use

Proprietary name: Maxipime.
Preparation: Injection.
Dosage: Adult, i.m., i.v., 1–6 g per day in 2–3 divided doses.
Available in USA, most of Europe and Japan; not available in the UK.

Side effects

It is used in the treatment of serious infections, particularly those in which resistant Gram-negative pathogens are known or suspected to be involved.

Chemical Synthesis

Cefepime, {6R-[6α,7β(Z)]}-1-[(7-{[(2-amino-4-thiazolyl)-(methoxyimino) acetyl]-amino}-2-carboxy-8-oxo-5-thia-1-(azabicyclo[4.2.0]oct-2-en-3-yl)methyl-1- methyl]pyrrolidine chloride (32.1.2.99), is synthesized by a combination of methods described for the synthesis of third-generation cephalosporins, in particular, cefaloridin (32.1.2.79) and ceftazidime (32.1.2.82).

Cefepime Preparation Products And Raw materials

Raw materials

Preparation Products


Cefepime Suppliers

Global( 155)Suppliers
Supplier Tel Fax Email Country ProdList Advantage
Henan DaKen Chemical CO.,LTD.
+86-371-66670886
info@dakenchem.com China 20914 58
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com CHINA 22607 55
Guangzhou PI PI Biotech Inc
+8618371201331
020-81716319 sales@pipitech.com;87478684@qq.com China 3245 55
Biochempartner
0086-13720134139
candy@biochempartner.com CHINA 968 58
Chongqing Chemdad Co., Ltd
+86-13650506873
sales@chemdad.com CHINA 37282 58
CONIER CHEM AND PHARMA LIMITED
86-18523575427
sales@conier.com CHINA 47498 58
career henan chemical co
13203830695 0086-371-86658258
0086-371-86658258 factory@coreychem.com CHINA 29864 58
Shaanxi Dideu Medichem Co. Ltd
15319487004
029-88380327 1015@dideu.com CHINA 4105 58
Hubei Ipure Biology Co., Ltd
+8618062405514
18062427325 ada@ipurechemical.com;ada@ipurechemical.com China 10352 58
Longyan Tianhua Biological Technology Co., Ltd
18039857276 0086 18039857276
javan@tianhuaapi.com CHINA 2791 58

View Lastest Price from Cefepime manufacturers

Image Release date Product Price Min. Order Purity Supply Ability Manufacturer
2021-07-01 Cefepime USP/EP/BP
88040-23-7
US $1.10 / g 1g 99.9% 100 Tons Min Dideu Industries Group Limited
2020-05-25 Cefepime
88040-23-7
US $0.00-0.00 / Kg 1KG 99.0%+ 300 MT Shaanxi Dideu Medichem Co. Ltd
2019-12-20 Cefepime
88040-23-7
US $1.00 / KG 1KG 95%~99% 1ton Career Henan Chemical Co

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