Cefuroxime axetil
Published: 23:51:08 November 21,2011 Views: 293
White or white powder, almost odorless, bitter taste. This product is soluble in acetone, dissolved in chloroform, methanol or ethanol in the slightly soluble, slightly soluble in ether, insoluble in water, the absorption coefficient This product is appropriate, accurately weighed, dissolved in methanol and containing 15μg per 1ml of the solution, according to spectrophotometry (Appendix Ⅳ A), was measured at 271nm wavelength absorption, the absorption coefficient (E1% 1cm) of 390 ~ 420.
Chemical category
β-lactam antibiotics, cephalosporins. 
Cefuroxime axetil
Chemical name (6R, 7R) -7 - [2 - furyl (methoxyimino) acetyl] -3 - methyl-carbamoyl oxygen -8-- oxo-5 - thia -1 - azabicyclo [4.2.0] -2-- ene-2 ??- carboxylic acid, 1 - acetoxy-ethyl Chemical Structure (see cefuroxime axetil capsule formula C20H22N4O10S MW 510.48 This product is fat-soluble pharmacokinetics strong, good oral absorption , absorbed rapidly in the intestinal mucosa and the portal circulation was non-specific esterase hydrolysis of cefuroxime, distribution to extracellular body fluid, serum protein binding rate is about 50%. postprandial oral administration of 250mg and 500mg, the blood peak plasma concentration (Cmax) was 2.5 to 3 hours to reach, were 4.1mg / L and 7.0mg / L. The product can promote the absorption of food, fasting and postprandial oral administration of absolute bioavailability of 37% and 52 %. 
Serum protein
Drinking milk can make the drug product - the value of area under the curve (AUC values ??increased, increasing the range of children's group is more significant than the adult group. The elimination half-life of blood products (t1 / 2 of 1.2 to 1.6 hours, compared with cephalosporins Crowe, cephalexin and cephradine slightly longer, neonatal and renal dysfunction in patients with t1 / 2 extension, older (average age 84 years serum t1 / 2 may be extended to about 3.5 hours fasting and postprandial oral administration of 500mg After 24-hour urinary excretion were dose volume of 32% and 48% of hemodialysis can reduce plasma concentrations of this product. Pharmacology and toxicology
This product is the acetyl ester of cefuroxime in vivo release of cefuroxime hydrolysis exert its antimicrobial activity, the product's mechanism of action, antimicrobial and antibacterial spectrum and cefuroxime are the same with other oral cephalosporins compared to the product of Gram-positive cocci, including pneumococci, A group (the role of hemolytic streptococcus and Staphylococcus aureus are not weak, while Gram-negative bacteria such as Neisseria gonorrhoeae, Haemophilus influenzae, the card he Mora bacteria and subjects such as the role of E. coli is better than cefaclor (cefaclor. product is the second-generation cephalosporins. absorbed through the gastrointestinal tract after oral administration, the role of the esterase rapidly hydrolyzed to cefuroxime play a role in antimicrobial . against Gram-positive cocci and activity similar to the first-generation cephalosporins, or slightly worse, but Staphylococcus aureus and gram-negative bacteria produce β-lactamase appeared to be quite stable in addition to methicillin-resistant Staphylococcus aureus, Enterococcus and Listeria spp, other positive bacteria (including anaerobic bacteria are sensitive to the chemicals in this product against Staphylococcus aureus antibacterial activity than cefazolin poor, 1 ~ 2mg / L of the product can be sensitive to penicillin and were inhibited All resistant Staphylococcus aureus. Haemophilus influenzae has strong antibacterial activity, Escherichia coli, Proteus mirabilis and other sensitive to the chemicals, indole-positive Proteus, citric acid, and Acinetobacter species on the product sensitivity is poor, the majority of drug-resistant Serratia, Pseudomonas aeruginosa, Campylobacter and Bacteroides fragilis resistant to the chemicals in this product's mechanism of action is inhibition of bacterial cell wall synthesis. This product is film-coated tablets, After removing the coating was white. [1] Adapt to the disease
This applies to goods hemolytic streptococcus, Staphylococcus aureus (excluding methicillin-resistant strains and Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and other Enterobacteriaceae caused by susceptible strains of adult acute pharyngitis or tonsillitis, acute otitis media, maxillary sinusitis, acute exacerbation of chronic bronchitis, acute bronchitis, simple urinary tract infections, skin and soft tissue infections and uncomplicated Neisseria gonorrhoeae urethritis and cervicitis. pharynx children inflammation or tonsillitis, acute otitis media and impetigo, etc. Dosage
Oral Adult general day 0.5g, lower respiratory tract infection: day 1g, simple urinary tract infection: day 0.25g. 2 sharing service 
Tonsil
With. Gonococcal urethritis simple single-dose therapy dose 1g.5 ~ 12-year-old children with acute pharyngitis or acute tonsillitis: body weight day 20mg/kg, 2 doses a day not more than 0.5g, acute otitis media , impetigo: body weight day 30mg/kg, 2 doses a day not more than 1g. Adverse reactions
The products are generally well tolerated, common adverse reactions are gastrointestinal reactions such as nausea, vomiting, diarrhea and loose stools, etc. occasionally pseudomembranous colitis. 
Rash
Chew tablets after the bitter because children are not welcome. Do not advocate for children under age 5, 1, common diarrhea, nausea and vomiting and other gastrointestinal reactions 2, a rare skin rash, drug fever and other allergic reactions. 3, occasionally pseudomembranous colitis, eosinophilia, elevated serum bilirubin, decreased hemoglobin, renal function, Coombs test was positive and a transient elevated liver enzymes. Major taboo
(1 of the goods and who are allergic to other cephalosporins, anaphylactic shock with penicillin or a history of immediate reactions and gastrointestinal malabsorption were banned. (Disabled children under the age of 25 pregnant women and lactating women (1 in animal experiments found no evidence of harmful to the fetus, but human studies lacked sufficient information, so only when there is a clear indication that pregnant women be careful using (2 product can be excreted by the milk, so breast-feeding women should be careful with or suspend breast-feeding. 
The digestive tract
Drug use in children under 5 years children should take cefuroxime axetil suspension in elderly patients older medication (mean age 84 years in patients with blood elimination half-life (t1 / 2 may be extended to about 3.5 hours, under the guidance of a doctor should be based on renal function adjust the dosage or medication interval. Note
1, the product with penicillin or cephamycins (cephamycins have cross-allergic reactions, so to penicillins, penicillin derivatives, penicillamine and cephamycins allergy caution. 2, renal dysfunction and liver dysfunction with caution. 
Liver cells
3, there is a history of gastrointestinal disease, particularly ulcerative colitis, enteritis, or antibiotic-associated colitis with caution. 4, long-term use product can cause flora imbalance, caused by secondary infections, such as occurred mild pseudomembranous colitis, withdrawal can be, but for the heavy holiday membranous colitis patients should be given symptomatic treatment and antibiotics against Clostridium difficile 5, the product should be taken after meals to increase absorption and improve the plasma concentration, and reduce the gastrointestinal tract. 6, this product should be swallowed, not chewed. 7, the interference of laboratory indexes: antiglobulin (Coombs test may be positive, copper sulfate urine sugar tests can be presented false positive, but the enzyme glucose test method is not affected, high-iron cyanide blood test may be false negative, but the enzyme glucose oxidase test method and the ascorbic acid test method is not affected, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and blood urea nitrogen can be increased, with Jaffe reaction for determination of serum and urine creatinine values ??may have a false increase FDA ban children under the age of 0.5, should take cefuroxime axetil suspension 8, animal studies found no evidence of harmful to the fetus, but human studies lacked sufficient information, so only when there is a clear indication that pregnant women be careful using this. 
Antiglobulin
9, the product can be discharged by the milk, so breast-feeding women should be used with caution or suspend breast-feeding in elderly (mean age 84 years the patient's blood elimination half-life (t1 / 2 (extended to about 3.5 hours, under the guidance of a doctor should be based on renal function to adjust the dosage or medication interval. Interaction
(1 furosemide, by Thani acid, bumetanide and other strong diuretic drugs, carmustine, streptozocin and other anti-tumor and renal toxicity of aminoglycoside antibiotics 
β-cell
Drugs combined with the product have increased the possibility of renal toxicity (2 clavulanic acid can enhance the product in some of the produce of the β-lactamase resistant to the chemicals while Gram-negative bacilli antimicrobial activity (3 and C of this product sulfur Shu drug combination will enable the goods - the value of area under the curve (AUC values ??increased by about 50% (4 products combined with antacids can reduce absorption of this product. Preparation specifications
(1) cefuroxime axetil tablets (2) capsules at C16H16N4O8S Cefuroxime axetil calculated (10.125g (20.25g 
Plasma protein
Drug Identification
1, recorded under the determination of the chromatogram for the test materials in the A, B isomer peak retention time with reference substance should be in A, B isomer peak retention time consistent. 
Chromatogram
2, the product of the infrared absorption spectrum should be consistent Cefuroxime ester reference substance of the map. Drug test
Crystallinity of this product, according to the determination (Appendix Ⅸ D), there should be no spaces and birefringence extinction. Isomer proper amount, according to assay method under test, B isomer peaks of the relative retention time of about to 0.85, A isomer peak relative retention time of 1.0. test chromatogram peak areas of isomers A and A, B isomer ratio of peak area and should be 0.48 ~ 0.55. to take the water products, according to the Determination of water (Appendix Ⅷ M first method A) determination of moisture content not over 1.5%. the proper amount of material, accurately weighed, add the mobile phase is made containing about 0.2mg per 1ml of the solution, as the test solution, precise amount of amount, plus the mobile phase per 1ml solution containing about 6μg, as a control solution. 
Serum
According to assay method under test, take control solution 20μl into the liquid chromatograph, adjust the sensitivity of the instrument, so that the main components of the recorder peak height of about 10% of full scale, and then take the test solution and control solution of 20μl, were injected into the liquid chromatograph, record the chromatogram to the peak retention time of 2.5 times the test solution, such as significant impurity peak, the amount of each impurity peak area and shall not make a big peak area of ??control solution. Residue on ignition to take This product is 1.0g, according to inspection (Appendix Ⅷ N), 0.2% had left no residue. Residue on ignition Heavy metals take the residue left under the law examination (Appendix Ⅷ H second law), not containing heavy metals than a million per twenty. Determination
According to high-performance liquid chromatography (Appendix Ⅴ D) were determined. Chromatographic conditions and system suitability test with octadecyl silane bonded silica as a filler to 0.2mol / L ammonium dihydrogen phosphate solution - methanol (62:38) as the mobile phase, detection wavelength of 278nm. take cefuroxime axetil appropriate reference substance, accurately weighed, dissolved in mobile phase (if necessary ultrasound treatment) and containing 0.2mg per 1ml of the solution, take this solution at 60 ℃ water bath for at least 1 
Cefuroxime axetil
Hours, that is, the relative retention time was about 1.2 cefuroxime axetil △ <2> - isomer, take 20μl into the liquid chromatograph, cefuroxime axetil A, B isomer between cefuroxime axetil A isomers and cefuroxime axetil △ <2> - separation between the isomers should be consistent with the provisions of Theoretical plate number by cefuroxime axetil isomer A peak calculation, should not be less than 1500. Determination to take the product is appropriate, accurately weighed (approximately equivalent to cefuroxime 50mg), set in 100ml volumetric flask, add methanol shaking, allows the dissolved and diluted to the mark, shake, precise amount of 10ml, 20ml volumetric flask set with mobile phase was diluted to the mark, shake, take 20μl into the liquid chromatograph, record the chromatograms, and the other to take cefuroxime axetil reference substance, the same method. by external standard method with peak area. Separation of impurities
Experimental
Instrument and reagent Japan Shimadzu HPLC CLASSLC10A, SPD10A UV detector, CR6A data processor. Cefuroxime axetil raw materials (in Guangzhou to provide a pharmaceutical), methanol (HPLC grade), ammonium dihydrogen phosphate (AR .) chromatographic conditions, DickmaC18 column (5μm, 150mm * 46mm), mobile phase A: 0.2mol / L ammonium dihydrogen phosphate solution, mobile phase B: methanol, flow rate, 1.3mL/min, gradient elution, detection wavelength , 278nm, injection volume, 20μL. Method results
Precision for the test materials 75mg, home 50mL volumetric flask, dissolved in methanol and diluted to the mark, shake, as for the test, another test solution for precision drawing 5mL, home 100mL flask, diluted with methanol to scale, home again draw 1mL 25mL volumetric flask, diluted with methanol to the mark, as the control solution, and the other to take methanol as a blank solution, each of 20μL, respectively, injection, gradient elution, 0 ~ 5min, mobile phase B increased from 15% to 35%, maintaining 10min, 60min, the mobile phase B is increased to 48%, 65min, the proportion of mobile phase B to 70 
Cefuroxime axetil product (8)%, maintained 5min, 75min, the proportion of mobile phase A to 85%, maintaining 10min. Than the standard method to calculate the impurity and total impurities. Experts to discuss
The main impurity is cefuroxime axetil cefuroxime axetil Δ3 isomer (thermal degradation of), and anti-isomers of cefuroxime axetil (photolysis), and various other by-products into the synthesis and other impurities According to reports, ICP has developed the drug to reach a consensus on the inspection of impurities: Any content greater than 0.1% in the control of impurities in principle, the list obviously, cefuroxime axetil raw materials, Δ3 isomer, anti-cephalosporin furosemide octyl isomer content are greater than 0.1%, the use of a closed set limits CHP2000 method, only control the total amount of impurities, has not made a single limit of impurity, it seems quite reasonable. BP2000 for several major impurity limits were provided for, but uses a simple normalization method, due to impurities and the main ingredients vary widely, it is difficult to accurately measure both the main components and impurities peak area peak area, and parameter settings, the large peak and peak area measurement accuracy of small effect can also cause calculation errors. Some experts suggested that the use of self-control method, both simple to overcome the shortcomings of normalization method, and solves the problem of the lack of reference substance impurities. 
Cefuroxime axetil
Sample solution, respectively, 1h at 60 ℃ water bath and 254nm UV irradiation 24h, mixed solution, respectively, and constant elution gradient elution separation method, the two methods can be isolated cefuroxime sulfate (isomer B, A), cefuroxime axetil Δ3 isomer, anti-cefuroxime axetil (isomer B, A) and other impurities. elution gradient elution method with better than the constant peak shape and separation, detachable more impurities, such as two @ cefuroxime ether isomers and other impurities. Cefuroxime axetil product (8)
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