What Factors Affect a Sufficient Cefazolin Dose?

Cefazolin is used for infections of the respiratory tract, urogenital system, skin and soft tissues, bones and joints, and biliary tract caused by sensitive bacteria. It can also be used for endocarditis, sepsis, pharynx and ear infections.

Cefazolin is used for infections of the respiratory tract, urogenital system, skin and soft tissues, bones and joints, and biliary tract caused by sensitive bacteria. It can also be used for endocarditis, sepsis, pharynx and ear infections.

Drug type

Essential medicines

Drug name

Cefazolin

English name

Cefazolin

Chinese alias

Oxazoline cephalosporins

English alias

Cefazoline; Cephazolin

Cefazolin Basic Information

Cefazolin drug name

Cefazolin

Cefazolin alias

Ceftizolin; pionemycin V; cephalosporin 5; pionezoline sodium; cefazolin; azoline cephalosporins;

Cefazolin English name

Cephazolin

Cefazolin alias

Cefazolin sodium; Ancef; Cefamedin; Kefzol; Totacef

Cefazolin chemical name

(6R, 7R) -3-[[(5-methyl-1,3,4-thiadiazol-2-yl) thio] methyl] -7-[(1H-tetrazol-1-yl) acetyl Amino] -8-oxo-5-thia-1-azabicyclo [4.2.o] oct-2-ene-2-carboxylic acid sodium salt

Cefazolin molecular structure

As shown on the right

Cefazolin molecular formula

C ₁₄ H ₁₃ N ₈ NaO ₄ S ₃

Cefazolin molecular weight

476

Physical and chemical properties of cefazolin

Its sodium salt is commonly used as a white or off-white crystalline powder. It is odorless, bitter, easily soluble in water, slightly soluble in methanol, and slightly soluble in ethanol. The pKa of the free acid is 2.5, and the pH of the solution is 4.5 to 6 (close to 5.5). The aqueous solution is relatively stable and can be stored at room temperature for 24 hours; the crystals precipitate out under cold conditions, and should be applied after being melted at warm temperature.

Cefazolin Pharmacopoeia Standard

[Identification] (1) In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution. (2) Take an appropriate amount of this product, dissolve and dilute with water to make a solution containing about 16 tons per ml. According to UV-visible spectrophotometry (Appendix IV A), it has a maximum absorption at a wavelength of 272nm. (3) The response of this product to the identification of sodium salt (1) (Appendix III).

[Check] Take this product for acidity, add water to make a solution containing 0.lg per lm l, determine according to the law (Appendix VI H), the pH value should be 4.5 ~ 6.5. Clarity and color of the solution: Take 5 parts of this product, each 0.6g. After adding 5ml of water to dissolve, the solution should be clear and colorless; if it is turbid, it must not be more concentrated than the turbidity standard solution (Appendix IX B). ; If the color is developed, it must not be deeper compared with the yellow or yellow-green standard colorimetric solution No. 3 (Appendix IX A, the first method). Relevant substances: take an appropriate amount of this product, add mobile phase A to dissolve and dilute to make a solution containing 2.5mg per lml as the test solution; take 1ml precisely, place it in a 100ml measuring flask, and dilute to the mark with mobile phase A Shake well as control solution. As determined by high performance liquid chromatography (Appendix VD), octadecylsilane-bonded silica gel was used as the filler; mobile phase A was phosphate buffer solution (take 2.91 g of disodium hydrogen phosphate dodecahydrate and 0.71 of potassium dihydrogen phosphate). g, dissolved with water and diluted to 1000 ml), mobile phase B is acetonitrile, flow rate is 1.2 ml per minute, linear gradient elution is performed according to the following table; column temperature is 45 ° C; detection wavelength is 254 nm. Take about 10mg of this product, add 10ml of 0.2% sodium hydroxide solution to dissolve, let stand for 15 ~ 30 minutes, accurately measure 1ml, put it into a 10ml measuring flask, add mobile phase A to dilute to the mark, shake well, impurities of cefazolin E reference substance and cefazolin impurity A reference substance, add the above solution to dissolve and dilute it to make a solution containing 0.1mg per 1ml, take 10l into the liquid chromatograph, press cefazolin impurity E, cefazolin The impurities A and cefazolin elute sequentially. The resolution between the cefazolin peak A and the cefazolin peak should not be less than 2.0, and the resolution between the cefazolin peak and the impurity peaks with relative retention times of about 0.97 and 1.05 should meet the requirements. Another 10µl of the control solution was injected into the liquid chromatograph, and the detection sensitivity was adjusted so that the peak height of the main component chromatographic peak was about 20% of the full scale. Precisely measure each 10fxl of the test solution and the control solution, and inject them into the liquid chromatograph, respectively, and record the chromatogram. If there is an impurity peak in the chromatogram of the test solution, the peak area of the cefazolin impurity A should not be greater than 0.5 times (0.5%) the main peak area of the control solution, and the peak areas of the cefazolin impurity E and other single impurities should not be larger than the main peak of the control solution. Area (1.0%). The sum of the peak areas of each impurity must not be greater than 3.5 times (3.5%) the area of the main peak of the control solution. Any peaks less than 0.05 times the area of the main peak of the control solution in the chromatogram of the test solution can be ignored.

Cefazolin polymer was determined by molecular exclusion chromatography (Appendix VH). Dextran gel 010 (40 ~ 120µm) was used as a filler for the chromatographic conditions and system suitability test. The inner diameter of the glass column was 1.0 to 1.4cm and the column length was 30 to 40cm. 0.lm0l / L phosphate buffer [0.lm0l / L disodium hydrogen phosphate solution-0.lm0l / L sodium dihydrogen phosphate solution (61:39)] at pH 7.0 as the mobile phase A, and water as Mobile phase B has a flow rate of approximately 1.5 ml per minute and a detection wavelength of 254 nm. Take 0.4mg / ml blue dextran 2 000 solution 100 ~ 200µl, and inject it into a liquid chromatograph, use mobile phase A, B as mobile phase to measure, record the chromatogram, the number of theoretical plates according to the blue dextran 2000 peak The calculations are not less than 400, and the tailing factor should be less than 2.0. The ratio of the retention time of the blue glucan 2000 peak in the two mobile phase systems should be between 0.93 and 1.07. The polymer peak in the main solution of the control solution and the test solution and the blue glucan 2000 peak in the corresponding chromatography system. The ratio of retention time should be between 0.93 and 1.07. Weigh about 0.2g of cefazolin sodium, put it into a 10ml measuring bottle, add 0.4mg / ml blue dextran 2000 solution to dissolve and dilute to the mark, and shake well. Take 100 ~ 200l into the liquid chromatograph, measure with mobile phase A, and record the chromatogram. The ratio of the peak height of the high polymer to the valley height between the monomer and the high polymer should be greater than 2.0. In addition, with mobile phase B as the mobile phase, 100 ~ 200µl of the control solution was accurately measured and the sample was injected 5 times continuously. The relative standard deviation of the peak area should not be greater than 5.0%. Weigh about 0.2g of this product in the determination method. Weigh it accurately, put it in a 10ml measuring bottle, add water to dissolve and dilute to the mark, shake well. Immediately and accurately measure 100 ~ 200l into the liquid chromatograph. Measure and record the chromatogram. In addition, precisely measure 100 ~ 200l of the control solution and inject it into the liquid chromatograph, and use mobile phase B as the mobile phase, and measure in the same way. Based on the peak area calculated by the external standard method, the polymer of cefazolin is based on cefazolin and should not exceed 0.04%. Take about 1g of the residual solvent acetone, put it into a 10ml volumetric flask, add water to dissolve and dilute to the mark, shake well, and use it as a test solution stock solution. Measure 1ml precisely, place it in the headspace bottle, add 1ml water precisely, shake well, and seal it as the test solution. Also accurately weigh 0.25g of acetone, place it in a 50ml measuring bottle, add water to dissolve and dilute to the mark, and shake well. Precisely measure 10ml, place it in a 100ml volumetric flask, dilute with water to the mark, shake well, and use it as a reference stock solution. Precisely measure 1ml of the reference stock solution, place it in the headspace bottle, and then precisely add 1ml of the test stock solution. Well, sealed, and used as the reference solution. Measured according to the residual solvent measurement method (Appendix P method 1). A capillary column with 100% dimethyl polysiloxane (or similar polarity) as the fixed liquid was used as the chromatographic column. The column temperature was 40 ° C and maintained for 12 minutes. Detector temperature is 250 ° C; inlet temperature is 200 ° C; headspace bottle equilibrium temperature is 70 ° C and equilibration time is 30 minutes; take the reference solution headspace sample and calculate the results of several injections, the relative The standard deviation must not exceed 5.0%. Take the test solution and the reference solution for headspace injection, record the chromatogram, and calculate the peak area according to the standard addition method, which should meet the requirements. Moisture is taken from this product and measured according to the moisture determination method (Appendix M -Method A). The moisture content must not exceed 2.5%. It can be seen that 5 parts of this product are taken, each 2.0g, each particle is checked for dissolution with water, and inspected according to law (Appendix H), which should meet the requirements. Take 3 parts of this product, add 50mg per 1ml of solution to the particle inspection water, and check according to the law (Appendix C). Each 1g sample contains more than 6,000 particles with a particle size of 10m or more. Over 600 capsules. Take this product for bacterial endotoxin and check it according to law (Appendix E). The test for endotoxin in 1mg of cefazolin should be less than 0.10EU. Take this product aseptically, after concentrating with a suitable solvent, transfer it to not less than 500ml of 0.9% sterile sodium chloride solution to dissolve it. After processing with membrane filtration method, check it according to law (Appendix H), and it should meet the requirements .

[Content determination] According to high performance liquid chromatography (Appendix VD). Chromatographic conditions and system suitability tests use octadecylsilane bonded silica gel as filler; disodium hydrogen phosphate and citric acid solution (take 1.33 g of anhydrous disodium hydrogen phosphate and 1.12 g of citric acid, dissolve with water and dissolve Dilute to 1000ml)-acetonitrile (88:12) as mobile phase; detection wavelength is 254nm; take about 10mg of this product, add 10ml of 0.2% sodium hydroxide solution to dissolve, let stand for 15-30 minutes, accurately measure 1ml, place In a 10ml volumetric flask, dilute to the mark with mobile phase, shake well, and take 10l into the liquid chromatograph. Record the chromatograph. The retention time of cefazolin peak is about 7.5 minutes. The resolution of cefazolin peak and adjacent impurity peaks should meet the requirements. The appropriate amount of this product is determined by the determination method, accurately weighed, and dissolved with mobile phase and quantitatively diluted to make a solution containing about 0.1mg per 1ml. Precisely measure 10l into the liquid chromatograph, and record the chromatogram; After adding 5ml of phosphate buffer solution (pH7.0) to dissolve the appropriate amount, it is quantitatively diluted with mobile phase to make a solution containing about 0.1mg per 1ml and measured in the same way. The content of C14H14N8O4S3 in the test sample was calculated by the peak area according to the external standard method.

[Category] -lactam antibiotics, cephalosporins.

[Storage] Tightly sealed, store in a cool, dark and dry place.

Cefazolin drug description

Cefazolin Pharmacology

It is a semi-synthetic first-generation cephalosporin. The antibacterial spectrum is similar to cephalexin, and it is effective against Staphylococcus (including enzyme-producing strains), Streptococcus (except Enterococcus), Streptococcus pneumoniae, E. coli, Proteus mirabilis, Klebsiella, Haemophilus influenzae, and Enterobacter aerogenes Has antibacterial effect. This product is characterized by a strong effect on Gram-negative bacteria and weak resistance to 13-lactamase from Staphylococcus. This product is usually used for injection. Intramuscular injection of lg gave a blood concentration of 64µg / ml for 1 hour; intravenous injection of lg gave a blood concentration of 106µg / ml for 30 minutes. This product has a long half-life (t1 / 2 = 1.8 hours), and the effective blood concentration is longer. Except for the brain tissue, it is well distributed throughout the body and the concentration in bile is low (1/5 ~ 1/2 of the serum drug concentration). This product is mainly excreted by the urine. 60% ~ 80% of the drug is excreted in the urine within 6 hours after intramuscular injection of 500mg. The peak urine concentration can reach 1000g / ml.

Cefazolin indications

Used for infections caused by sensitive bacteria in the respiratory tract, urogenital system, skin and soft tissues, bones and joints, and biliary tract. It can also be used for endocarditis, sepsis, pharynx and ear infections.

Cefazolin usage and dosage

Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.

Cefazolin adverse reactions

Allergic reactions such as rash, erythema, drug fever, bronchospasm are common, and occasional anaphylactic shock is seen. Gastrointestinal reactions have symptoms such as nausea, vomiting, loss of appetite, abdominal pain, diarrhea, taste disorders, and occasionally pseudomembranous enteritis. There may be temporary liver dysfunction after medication. A small number of patients may have reduced hemoglobin, thrombocytopenia, neutropenia, and eosinophilia. Occasionally, hemolytic anemia affects the kidneys. A small number of patients may have elevated urea nitrogen, creatine, and creatinine.

Cefazolin contraindications

Those who are allergic to cephalosporins are prohibited.

Cefazolin precautions

(1) Those who are allergic to penicillin and those with liver and kidney dysfunction should be used with caution. (2) Intramuscular injection can cause local pain, and intravenous injection can cause phlebitis. (3) Some injections for intramuscular injection contain lidocaine and cannot be injected into veins.

Cefazolin drug interactions

(1) Combined with gentamicin or amikacin, it has a synergistic antibacterial effect on some sensitive strains. (2) Combined with probenecid, it can inhibit the excretion of this product in the kidney and increase the blood concentration by about 30%. (3) Equivalent to nephrotoxic drugs such as strong diuretics, aminoglycosides, and antitumor drugs, which can increase nephrotoxicity. (4) Use with warfarin can increase the risk of bleeding.

Cefazolin poisoning

Cefazolin (pionemycin V) is a first-generation cephalosporin with a strong antibacterial effect. It is used to treat respiratory tract infections, urinary tract infections, skin and soft tissue infections, osteomyelitis, eye, ear, nose, and throat infections caused by sensitive bacteria , Hepatobiliary infections and gynecological infections. Poor gastrointestinal absorption, intramuscular or intravenous administration, plasma protein binding rate of 74% to 86%, half-life of 1.8h. For severe infections, 6g can be used daily.

Clinical manifestation

1. Other adverse reactions in treatment are similar to cephalexin.

2. The incidence of local pain during intramuscular injection is 5% to 15%. Thrombophlebitis occurs in about 4% of patients during intravenous injection.

3. Patients with impaired renal function who used the drug 12g / d, there have been reports of encephalopathy. Patients with uremia may develop coagulopathy with this drug.

treatment

The main points of treatment for cefazolinosis are:

1. Hemodialysis for 6 hours can reduce the blood concentration of this drug by 40% to 45%.

2. The principle of treatment is the same as that of cephalexin ^[1] .

Cefazolin preparation

Sterile powder for injection: 0.5g, 1.0g

^[2-5]