Cefepime

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H302：Gesundheitsschädlich bei Verschlucken.

• Sicherheit

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

  P305+P351+P338：BEI KONTAKT MIT DEN AUGEN: Einige Minuten lang behutsam mit Wasser spülen. Eventuell vorhandene Kontaktlinsen nach Möglichkeit entfernen. Weiter spülen.

Cefepime Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
  R42/43:Sensibilisierung durch Einatmen und Hautkontakt möglich.

• S-Sätze Betriebsanweisung:

  S22:Staub nicht einatmen.
  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
  S36/37/39:Bei der Arbeit geeignete Schutzkleidung,Schutzhandschuhe und Schutzbrille/Gesichtsschutz tragen.

• Beschreibung

  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.

• Chemische Eigenschaften

  colorless Powder

• Originator

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

• Verwenden

  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.

• Definition

  ChEBI: Cefepime is a cephalosporin bearing (1-methylpyrrolidinium-1-yl)methyl and (2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetamido groups at positions 3 and 7, respectively, of the cephem skeleton. It has a role as an antibacterial drug. It is a cephalosporin and an oxime O-ether. It is a conjugate base of a cefepime(1+).

• 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-tritylamin

• Trademarks

  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.

• Pharmakokinetik

  C_{max 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.

• Nebenwirkungen

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

• Synthese

  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 Upstream-Materialien And Downstream Produkte

Cefepime Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(185)Suppliers

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