Ceftizoxime sodium

Description

Ceftizoxime was synthesized by Fujisawa Pharmaceutical Industries in 1979. It possesses the (iminothiazolyl)methoxyiminomethyl group at the 7 position of the cephem nucleus, but there is no side chain at the 3 position. The compound shows excellent activity against gram-positive and gram-negative bacteria, behavior similar to that of cefotaxime. Unlike cefotaxime, however, it is not metabolized in vivo.

Chemical properties

Cefotaxime Sodium is white, white or light yellow crystalline powder; odorless; insoluble in organic solvents but soluble in water. The 10% solution has a pH of 4.5 to 6.5. Dilute solution is colorless or yellowish while high-concentration solution is grayish yellow. Dark yellow or brown color indicates that the drug has been deteriorated. The aqueous solution can be stored at 5 ℃ for 1 week.

Originator

Eposelin,Fujisawa,Japan,1982

The Uses of Ceftizoxime sodium

Antibacterial.

The Uses of Ceftizoxime sodium

A broad spectrum antibiotic targeting a wide variety of Gram-positive and Gram-negative bacteria

Definition

ChEBI: The sodium salt of ceftizoxime.

Manufacturing Process

Phosphorus oxychloride (2.0 g) was added at one time at 5°C to 10°C to a suspension of 2-methoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetic acid (syn isomer) (2 g) in dry ethyl acetate (20 ml). After stirring for 20 minutes at 7°C to 10°C, bis(trimethylsilyl)acetamide (0.4 g) was added thereto at the same temperature. After stirring for 10 minutes at 7°C to 10°C, phosphorus oxychloride (2.0 g) was dropwise added thereto at the same temperature. The resulting mixture was stirred for 10 minutes at 7°C to 10°C, and dry dimethylformamide (0.8 g) was dropwise added thereto at the same temperature. The mixture was stirred for 30 minutes at 7°C to 10°C to give a clear solution. On the other hand, trimethylsilylacetamide (7.35 g) was added to a suspension of 7-aminocephalosporanic acid (2.45 g) in dry ethyl acetate (8 ml), after which the mixture was stirred at 40°C to give a clear solution.
To this solution was added at one time the above-obtained ethyl acetate solution at -15°C, and the resulting mixture was stirred for 1 hour at -10°C to -15°C. The reaction mixture was cooled to -30°C, and water (80 ml) was added thereto. The aqueous layer was separated, adjusted to pH 4.5 with sodium bicarbonate and subjected to column chromatography on Diaion HP-20 resin (Mitsubishi Chemical Industries Ltd.) using 25% aqueous solution of isopropyl alcohol as an eluent. The eluate was lyophilized to give 7-[2- methoxyimino-2-(2-amino-1,3-thiazol-4-yl)acetamido]cephalosporanic acid (syn isomer) (1.8 g), MP 227°C (decomp.).

brand name

Cefizox (Astellas).

Therapeutic Function

Antibacterial

Clinical Use

Ceftizoxime (Cefizox) is a third-generation cephalosporinthat was introduced in 1984. This β-lactamase–resistant agentexhibits excellent activity against the Enterobacteriaceae,especially E. coli, K. pneumoniae, E. cloacae, Enterobacteraerogenes, indole-positive and indole-negative Proteus spp.,and S. marcescens. Ceftizoxime is claimed to be more activethan cefoxitin against B. fragilis. It is also very active againstGram-positive bacteria. Its activity against P. aeruginosa issomewhat variable and lower than that of either cefotaxime orcefoperazone.
Ceftizoxime is not metabolized in vivo. It is excretedlargely unchanged in the urine. Adequate levels of the drugare achieved in the cerebrospinal fluid for the treatment ofGram-negative or Gram-positive bacterial meningitis. It mustbe administered on a thrice-daily dosing schedule because ofits relatively short half-life. Ceftizoxime sodium is very stablein the dry state. Solutions maintain potency for up to 24hours at room temperature and 10 days when refrigerated.