Pharmacokinetics |
Cefoperazone is not easily absorbed orally, but can be rapidly distributed to the blood, bile,
urine, liver and brain tissues after injection. The highest drug concentration is found in bile and urine,
which is 60 to 300 times the blood drug concentration.t1/2 is 2h. PBP is 90%. In patients with poor liver
function or bile duct obstruction,t1/2 is extended to 4 to 8h, and the cerebrospinal fluid can
reach therapeuticconcentrations in meningitis.Most of it is excreted in urine and bile in its original form. |
Drug Interactions |
1. When cefoperazone is used simultaneously with drugs that can produce hypoprothrombinemia, thrombocytopenia
or gastrointestinal ulcer bleeding,the cumulative or multiple effects of these drugs on coagulation function
and bleeding risk should be considered.
2. Do not take alcoholic beverages or drink alcohol during medication, otherwise it may cause a disulfiram-like reaction |
Preparation |
A new method for synthesizing a sodium cefoperazone compound comprises the following steps:
1) suspending 7-ACA in a mixture of dimethyl carbonate, glacial acetic acid and a trifluoride boron carbonate dimethyl ester complex,
then adding 1-methyl-5-thiotetrazolyl for reaction, and obtaining solid TZA after crystallization;
2) suspending TZA in an organic solvent,adding hexamethyldisilazane for reflux and setting aside;
then dissolving hydroxypiperazine in a mixture of N, N-dimethylacetamide and the above organic solvent,
cooling, and adding phosphorus oxychloride for reaction; adding TZA reflux solution dropwise to
hydroxypiperazine acyl chloride solution to startcondensation reaction, and obtaining cefoperazone acid after crystallization;
3) dissolving cefoperazone acid in a mixture of acetone and water, adding alkali
solution dropwise to a pH value of 7.0, stirring for reaction, quickly adding acetone for crystallization,
and then filtering, washing with acetone, and drying to obtain a white solid of sodium cefoperazone. |
Indications |
Cefoperazone is used for infections of the upper and lower respiratory tract, bile duct, urinary tract,
genitals, bones and joints, skin and soft tissues, sepsis, meningitis, peritonitis, otitis media, gonorrhea, etc.
caused by sensitive bacteria. |
Chemical properties |
White or off-white crystalline powder, odorless, slightly bitter. Hygroscopic. Soluble in acetone or dimethyl sulfoxide, slightly soluble in methanol or ethanol,
very slightly soluble in ethyl acetate or water. [α]D20-30°～-38°(30mg of this product is dissolved in 1ml of a solution consisting of
phosphate buffer (1mol/L potassium dihydrogen phosphate solution is diluted with 10mol/L potassium hydroxide solution to a Ph value of 6.0) and acetonitrile (90:10)).
Stable at Ph=4.0～7.0, slightly unstable in acidic conditions, and very unstable in alkaline conditions. Melting point 169171℃ (hydrate).
Cefoperazone sodium (CefoperazoneSC, diuHl): C25H26N9O8S2Na. [62893-20-3]. White or off-white crystalline powder, odorless, bitter. Hygroscopic.
It is easily soluble in water, slightly soluble in methanol, very slightly soluble in ethanol, insoluble in ethyl acetate, chloroform, ether,
acetone and n-hexane. Melting point 180°C (decomposition) [α] D20-15°～-25° (10 mg of this product is soluble in 1 ml of water). |
Uses |
Third-generation cephalosporin broad-spectrum antibiotics, bactericidal against a variety of gram-positive and gram-negative bacteria,
more active against Pseudomonas aeruginosa than other cephalosporins, very stable against β-lactamase, and must be administered by injection.
Chemicalbook is clinically used to treat sepsis, respiratory infections, biliary tract infections, urinary tract infections,
reproductive system infections, skin and soft tissue infections, etc. |
Uses |
It is a semi-synthetic broad-spectrum antibiotic with an antibacterial spectrum similar to that of ceftriaxone |
Production method |
Method 1: Under nitrogen protection, 0℃ and stirring, add 1-methyl-5-mercapto-1,2,3,4-tetrazolyl to the boron trifluoride monoether complex,
cool to -5℃, then add 7-ACA in batches, raise to 25℃ and react for 2h. Add p-toluenesulfonic acid monohydrate at 15-20℃,
then drop 6mol/L hydrochloric acid, stir at 20℃ and 0-5℃ for 1h each. Filter the crystals, wash with acetonitrile-acetone twice, and obtain compound (I)
with a yield of 82%. Compound (I) is dissolved in dimethylacetamide (DMA), and trimethylchlorosilane is added dropwise at 10℃ and stirring,
and stirred at 25℃ for 1h to obtain a solution of compound (I), which is directly used in the next step. Compound (II) is dissolved in DMA, phosphorus
oxychloride is added dropwise at -20℃, and stirred for 2h. Drop the solution of compound (I) mentioned above in Chemicalbook and stir for 1h. Raise to 20℃,
add sodium bicarbonate in batches to control the Ph value of the reaction solution to 2. Add water and stir for 2h. Under vigorous stirring,
slowly pour the reaction solution into water. Filter the solid, recrystallize with acetonitrile-water to obtain white cefoperazone crystals with a yield of
52.3% and a melting point of 169-171℃. [α]D23-35.5°. Using 7-ACA as a raw material, first react with 5-mercapto-1-methyl-tetrazolyl to generate a 3-substituted
7-ATCA intermediate, and then condense with α-(p-hydroxyphenyl)-α-[(4-ethyl-2,3-dioxo-1-pyrazinyl)formamido]acetyl chloride, adjust the Ph value by
acidification to make cefoperazone free acid crystals, dissolve with sodium bicarbonate to obtain the sodium salt of cefoperazone. |
Method 2: 3.0g 7-[(D)-2-amino-2-p-hydroxyphenylacetamido]-3-[[(1-methyl-1,2,3,4-tetrazolyl-5-yl)sulfur]methyl]cephem-4-carboxylic
acid is suspended in 29ml water and 0.95g anhydrous potassium carbonate is added. When the insoluble matter is completely dissolved,
15ml ethyl acetate is added,and then 1.35g 4-ethyl-2,3-dioxopyrazinecarboxylic acid chloride is added at 0-5℃ for 15min,
and the reaction is continued at 0-5℃ for 30min. After the reaction is completed, 40ml ethyl acetate and 10ml
acetone are added to the separated water layer,and the pH is adjusted to 2.0 with dilute hydrochloric acid. The organic layer is separated,
washed twice with 10ml water, dried over anhydrous magnesium sulfate, and the solvent is evaporated under reduced pressure.
The residue is dissolved in 10ml acetone, and 60ml isopropanol is added to produce crystals. The crystals were collected by filtration,
washed with isopropanol and dried to obtain 3.27 g of cefoperazone with a yield of 80.7% and a melting point of 188-190°C (decomposition). |
