What Factors Affect a Sufficient Cefdinir Dose?

The chemical name of cefdinir is (6R, 7R) -7-[[(2-amino-4-thiazolyl)-(oxime) acetyl] amino] -3-vinyl-8-oxo- 5-thia-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, slightly yellow to yellow crystalline powder; slightly smelly. This product is slightly soluble in 0.1 mol / L phosphate buffer solution [0.1 mol / L disodium hydrogen phosphate solution-0.1 mol / L potassium dihydrogen phosphate solution (2; 1)], and insoluble in water, ethanol or ether. The molecular formula is C14H13N5O5S2, molecular weight is 395.41400, density is 1.89 g / cm, melting point is> 180 ° C dec.

Chinese name: Cefdinir
Foreign name: cefdinir

CAS number: 91832-40-5
Molecular formula: C14H13N5O5S2

About Cefdinir Compounds

Cefdinir Basic Information

Chinese name cefodinil

English name: cefdinir

English alias: Omnice; Cefdinir; Cefzon; Novacef; cefdinyl;

CAS number: 91832-40-5

Molecular formula: C ₁₄ H ₁₃ N ₅ O ₅ S ₂

Molecular weight: 395.41400

Structural formula:

Exact mass: 395.03600

PSA: 211.75000

LogP: 0.73820 ^[1]

Cefdinir physicochemical properties

Appearance and properties: white powder

Density: 1.89 g / cm3

Melting point:> 180 ° C dec.

Refractive index: 1.861

Storage conditions: room temperature ^[1]

Cefdinir molecular structure data

1. Molar refractive index: 90.94

2. Molar volume (cm / mol): 210.2

3. Isotonic specific volume (90.2K): 640.0

4. Surface tension (dyne / cm): 85.8

5. Polarizability (10-24cm3): 36.05 ^[2]

Cefdinir production method

With 7-ACA as the raw material, after protecting the 7-amino group and the 2-carboxy group, it is reacted with triphenyl phosphorus to obtain a phosphide.It is subjected to Wittig reaction with formaldehyde under basic conditions to obtain a vinyl derivative at the 3-position (I ). Treatment with hydrochloric acid frees the amino group at position 7 to obtain compound (II). In the presence of N-trimethylsilylacetamide, compound (II) and 4-bromoacetoacetyl bromide were reacted in ethyl acetate at -10 ° C for 1 h to obtain the acylated product (III) in a yield of 88%. . Compound (III) was dinitrosated with dichloromethane and acetic acid with an aqueous solution of sodium nitrite at -5 ° C for 30 min, and then urea was added to destroy the excess sodium nitrite to obtain a quantitative yield of hydroxylamine compound (IV). Compound (IV) is reacted with thiourea in N, N-dimethylacetamide at 5 ° C for 1 h and cyclized to obtain compound (V). The crude compound (V) was reacted in anisole with trifluoroacetic acid at 5 ° C for 1 h, and then recrystallized with water to obtain cefdinir. ^[1]

Cefdinir uses

This product is a third-generation oral cephalosporin. ^[1]

Cefdinir Pharmacopoeia Standard

Cefdinir source (name), content (potency)

This product is (6R, 7R) -7-[[(2-amino-4-thiazolyl)-(oxime) acetyl] amino] -3-vinyl-8-oxo-5-thia-1 -Azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid. Calculated as anhydrous, cefdinir (C ₁₄ H ₁₃ N ₅ O ₅ S ₂ ) should not be less than 94.0%. ^[3]

Cefdinir traits

This product is slightly yellow to yellow crystalline powder; it has a slight odor.

This product is slightly soluble in 0.1 mol / L phosphate buffer solution [0.1 mol / L disodium hydrogen phosphate solution-0.1 mol / L potassium dihydrogen phosphate solution (2; 1)], and insoluble in water, ethanol or ether.

Specific rotation

Take this product, weigh it accurately, add the above 0.1mol / L phosphate buffer solution to dissolve and quantitatively dilute it to make a solution containing about 10mg per 1ml, and measure it according to law. The specific rotation is -58 ° to -66 °.

Absorption coefficient

Take this product, weigh it accurately, add the above 0.1mol / L phosphate buffer solution to dissolve and quantitatively dilute it to make a solution containing about 10g per 1ml, according to the ultraviolet-visible spectrophotometry (Appendix IVA of the Pharmacopoeia Part II of the 2010 edition) The absorbance was measured at a wavelength of 287 nm, and the absorption coefficient was 570 to 610. ^[3]

Cefdinir 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) The infrared light absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Drugs" 1122). ^[3]

Cefdinir Exam

Crystallinity

Take this product a little, check it according to law, and it should meet the requirements.

acidity

Take about 0.2g of this product and add 20ml of water to make a homogeneous suspension. According to law, the pH value should be 2.5 ~ 4.5.

relative substance

Take about 37.5mg of this product, put it in a brown measuring bottle, add 4ml of the above 0.1mol / L phosphate buffer solution to dissolve, add mobile phase A and dilute to make a solution containing about 1.5mg per 1ml, as the test solution; Take a precise amount of 1ml, put it into a 100ml measuring flask, add mobile phase A to dilute to the mark, shake well, and use it as a control solution. As determined by high performance liquid chromatography, octadecylsilane bonded silica gel was used as the filler; mobile phase A was a 0.25% tetramethylammonium hydroxide solution (the pH was adjusted to 5.5 with phosphoric acid), and 0.1 mol was added per 1000 ml. / L ethylenediamine tetraacetic acid disodium solution 0.4ml; mobile phase B is 0.25% tetramethylammonium hydroxide solution (pH adjusted to 5.5 with phosphoric acid)-acetonitrile-methanol (500: 300: 200), each in 1000ml Add 0.1 mol / L ethylenediamine tetraacetic acid disodium solution 0.4ml. Linear gradient elution was performed according to the following table. The column temperature was 40 ° C and the detection wavelength was 254nm. Take about 37.5mg of cefdinir reference product and place it in a 25ml volumetric flask, add 4ml of the above 0.1mol / L phosphate buffer to dissolve, dilute to the mark with mobile phase A, shake well, and heat in a water bath for no less than 30 minutes Let it cool down to get a mixed solution containing about 1.5mg of cefdinir and its degradation impurities per 1ml (of which the relative main peak retention time is 0.95 and the amount of impurities at 1.1 are about 2% each). Take 20l into the liquid chromatograph and record In the chromatogram, the retention time of cefdinir peak is about 22 minutes, the retention time of E-isomer peak is about 1.5 times the retention time of cefdinir peak, and the separation of cefdinir peak and its relative retention time at 0.95 and 1.1 impurity peaks. The degree should not be less than 1.0. Take 20l of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the chromatographic peak of the main component is about 20% of the full scale, and accurately measure 20l each of the test solution and the control solution, and inject them into the liquid chromatograph. Record the chromatogram. If there are impurity peaks in the chromatogram of the test solution, the E-isomer peak area must not be greater than 0.5 times (0.5%) the main peak area of the control solution, and the area of a single impurity peak must not be greater than the main peak area (1.0%) of the control solution. The peak area should not be greater than 3 times (3.0%) the main peak area of the control solution. Any peaks smaller than 0.05 times the main peak area of the control solution in the chromatogram of the test solution can be ignored.

Time (minutes)	Mobile phase A (%)	Mobile phase B (%)
0	95	5
2	95	5
twenty two	75	25
32	50	50
37	50	50
38	95	5
48	95	5

Moisture

Take this product, add a mixed solution of formamide and methanol (2: 1) to dissolve it, and measure according to the moisture measurement method (2010 edition Pharmacopoeia Part II Appendix M first method A), the moisture content must not exceed 2.0%.

Residue on ignition

Take 1.0g of this product and inspect it according to law. The residual residue should not exceed 0.2%.

Heavy metal

Take the residue left under the item of burning residue and inspect it according to law. The content of heavy metals must not exceed 10 parts per million. ^[3]

Determination of cefdinir content

As determined by high performance liquid chromatography.

Chromatographic conditions and system suitability tests

Octadecylsilane-bonded silica gel as filler; 0.25% tetramethylammonium hydroxide solution (pH adjusted to 5.5 with phosphoric acid)-acetonitrile-methanol (900: 60: 40), add 0.1mol per 1000ml / L ethylenediamine tetraacetic acid disodium solution 0.4ml was used as the mobile phase; the detection wavelength was 254nm. Take about 20mg of cefdinir reference product, put it into a 100ml volumetric flask, add 2ml of the above 0.1mol / L phosphate buffer to dissolve, dilute to the mark with mobile phase, shake well, and heat in a water bath for no less than 30 minutes. Cold, get a mixed solution containing about 0.2mg of cefdinir and its degradation impurities per 1ml (where the relative main peak retention time is 0.9% and the amount of impurities at about 1.2% each is about 2%), take 20l into the liquid chromatograph, record the chromatogram The retention time of the cefdinir peak is about 8 minutes, the retention time of the E-isomer peak is about 3.5 times the retention time of the cefdinir peak, and the resolution of the cefdinir peak and the relative retention time of the impurity peaks at 0.9 and 1.2 are equal. Should not be less than 1.2.

Assay

Take about 20mg of this product, accurately weigh it, place it in a 100ml brown measuring flask, add 2ml of the above 0.1mol / L phosphate buffer solution to dissolve, dilute to the mark with mobile phase, shake well, and accurately take 20l into the liquid chromatograph Record the chromatogram; take an appropriate amount of cefdinir reference and measure the same method. Calculate the peak area according to the external standard method. ^[3]

Cefdinir Compound Related Drugs

Cefdinir drug name:

[Common name] Cefdinir dispersible tablets

[English name] Cefdinir Dispersible Tablets

[Chinese Pinyin] Tou Bao Di Ni Fen San Pian ^[4]

Cefdinir Ingredients:

The main ingredient of this product is cefdinir. Chemical name: [6R-7R] -7-[[(2-amino-4-thiazolyl)-(oxime) acetyl] amino] -3-vinyl-8-oxyl -5-Thaza-1-azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid ^[4]

Cefdinir belongs to category:

Chemical Drugs and Biological Products >> Antimicrobials >> Antibacterials >> Antibiotics ^[4]

Cefdinir traits:

This product is slightly yellow to yellow flakes. ^[4]

Cefdinir indications:

Staphylococcus, Streptococcus, Pneumococcus, Streptococcus, Propionibacterium, Neisseria Gonorrhoeae, Moraxella, Escherichia coli, Klebsiella, Singular Deformation The following infections caused by strains such as Bacillus, Providence, Haemophilus influenzae:
· Laryngitis, tonsillitis, acute bronchitis, pneumonia;
Otitis media, sinusitis;
· Pyelonephritis, cystitis, gonococcal urethritis;
Attachment inflammation, intrauterine infection, vestibular glandular inflammation;
· Secondary infections of mastitis, perianal abscess, trauma or surgical wound;
· Folliculitis, carbuncle, bloated, carbuncle, infectious impetigo, erysipelas, cellulitis, lymphangitis, paronychia, subcutaneous abscesses, pediculoma infections, chronic abscess;
· Blepharitis, stye, meibomitis. ^[4]

Cefdinir Specifications:

100mg ^[4]

Cefdinir Dosage:

Dispersed in water orally or swallowed directly.
The usual dose for adults is 100 mg once, three times a day.
The usual dose for children is 9-18 mg / kg daily, orally in three divided doses.
The dose can be increased or decreased by age, symptoms, or as prescribed by your doctor. ^[4]

Cefdinir adverse reactions:

According to foreign clinical trial data, of the 13,715 patients treated with this product, 354 (2.58%) adverse reactions (including abnormal laboratory data) were reported. The main adverse reactions were gastrointestinal symptoms (110 cases, 0.80%), such as diarrhea or abdominal pain; skin symptoms (31 cases, 0.23%), such as rash or itching. The main laboratory data abnormalities included elevated alanine aminotransferase (126 cases, 0.92%) and aspartate aminotransferase (89 cases, 0.65%); eosinophilia increased (41 cases, 0.30%).
Clinical adverse reaction

Note: If the above symptoms occur, the drug should be stopped immediately and treated appropriately.
2. Other adverse reactions 1) Dermatology: history-about syndrome (<0.1%) or toxic epidermal necrolysis (<0.1%) may occur. Patients should be closely observed. If fever, headache, arthralgia, erythema / blister appears on the skin or mucous membrane, skin feels tight / burning / pain, the medicine should be stopped immediately and treated appropriately.
2) Allergic reactions: Allergic reactions may occur, such as dyspnea, erythema, angioedema, urticaria, the incidence rate is <0.1%. Patients should be closely observed, and if abnormal conditions occur, the drug should be stopped immediately and treated appropriately.
3) Shock: Shock may occur with an incidence rate of <0.1%. Patients should be closely observed. If symptoms such as discomfort, mouth discomfort, wheezing, dizziness, constipation, tinnitus, or sweating occur, the drug should be discontinued immediately and treated appropriately.
4) Hematology: pancytopenia (<0.1%), agranulocytosis (<0.1%, initial symptoms are fever, sore throat, headache, discomfort), thrombocytopenia (<0.1%, initial symptoms are Bruises, purpura) or hemolytic anemia (<0.1%, initial symptoms are fever, hemoglobinuria, anemia symptoms). Patients should be closely observed, and if abnormal conditions occur, the drug should be stopped immediately and treated appropriately.
5) Colitis: Severe colitis (<0.1%) may occur, such as pseudomembranous colitis confirmed by blood. Patients should be closely observed. If symptoms such as abdominal pain or frequent diarrhea occur, the drug should be discontinued immediately and treated appropriately.
6) Interstitial pneumonia or PIE syndrome: Interstitial pneumonia or PIE syndrome (<0.1%) may be confirmed by fever, cough, dyspnea, abnormal chest X-rays, or eosinophilia. If such symptoms occur, the drug should be discontinued immediately and treated appropriately, such as the use of adrenal corticosteroids.
7) Kidney disease: Severe kidney disease (<0.1%) may occur, such as acute renal failure. Patients should be closely observed, and if abnormal conditions occur, the drug should be stopped immediately and treated appropriately.
8) Fulminant hepatitis, liver dysfunction, or jaundice: Severe hepatitis (<0.1%) may occur, such as fulminant hepatitis with abnormal elevations of alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase (<0.1) %) Or jaundice (<0.1%). Patients should be closely observed, and if abnormal conditions occur, the drug should be stopped immediately and treated appropriately. ^[4]

Cefdinir contraindications:

Those who have a history of shock for this product are banned, and those who are allergic to penicillin or cephalosporin should be used with caution.

Precautions:

According to the practice, after determining the susceptibility of microorganisms to this product, the course of treatment of this product should be limited to the shortest period required to treat patients to prevent the generation of drug-resistant bacteria.
It is recommended to avoid using with iron preparations. If combined use cannot be avoided, iron preparations should be used 3 hours after taking this product.
Because of the possibility of allergic reactions such as shock, you should ask your allergy history in detail.
The following patients should be used with caution-those with a history of allergies to penicillin antibiotics;
I or my relatives are prone to allergic symptoms such as bronchial asthma, rash, urticaria;
-Patients with severe renal dysfunction: Because cefdinir exists in the serum of patients with severe renal dysfunction for a long time, the dose should be reduced according to the severity of renal dysfunction and the interval between dosing should be prolonged. For patients undergoing hemodialysis, the recommended dose is 100 mg once a day;
-Patients with severe underlying diseases, those who cannot eat well or take oral nutrition, elderly people, cachexia, etc. (due to the occurrence of vitamin K deficiency, close clinical observation is required).
Impact on clinical test values-In addition to the test strip urine test, false positives may occur when urine tests are performed using the Benedict reagent, Fehling reagent, and Clinitest test.
Positive direct serum antiglobulin test may occur, so be careful.
Other considerations-Red stool may appear when used with iron-added products such as milk powder or enteral nutrition.
Red urine may appear. ^[4]

Cefdinir medication for pregnant and lactating women:

Regarding medication during pregnancy, its safety has not been established. For pregnant women or women suspected of having a pregnancy, the drug should be weighed against the pros and cons, and can only be used if the advantages outweigh the disadvantages.
Medications for lactating women should be weighed against pros and cons, and should only be used if the pros outweigh the disadvantages. ^[4]

Cefdinir medication for children:

Medication safety for premature infants and newborns with underweight has not been established. ^[4]

Cefdinir medication for the elderly:

Elderly patients should pay special attention to the following aspects when using this product, and adjust the dose and dosing interval according to the clinical observation of the patient:
1. Due to physical decline, elderly patients may be prone to adverse reactions.
2. Due to vitamin K deficiency, elderly patients may have a tendency to bleed. ^[4]

Cefdinir Drug Interactions:

This product should be used with caution in combination with the following drugs.

Overdose:

Overdose use of cefdinir has not been studied. In studies of acute, toxic, and erosive ulcers, a single oral dose of 5600 mg / kg did not produce side effects. Other beta-lactam antibiotics may show the following side effects when overdose: nausea, vomiting, diarrhea, and convulsions. Serum dialysis can remove cefdinir from the body. Hemodialysis is useful in patients with toxic reactions caused by overdose, especially in patients with renal insufficiency. ^[4]

Cefdinir pharmacology and toxicology:

Pharmacological and antibacterial effects-It has a wide range of antibacterial spectrum against Gram-positive bacteria and Gram-negative bacteria, especially Staphylococcus and Streptococcus among Gram-positive bacteria, which are more effective than conventional oral cephalosporins Strong antibacterial activity, its mode of action is bactericidal.
-It is stable to -lactamase produced by various bacteria, and has excellent antibacterial activity against -lactamase producing bacteria.
· Mechanism of action The mechanism of action is to prevent the synthesis of bacterial cell walls. It has strong affinity for penicillin-binding proteins (PBP) 1 (1a, 1bs), 2, 3, but has different active sites for different bacteria.
Toxicological studies Acute and chronic toxicity studies of cefdinir in experimental animals such as rats and dogs have shown that cefdinir is well tolerated. Cefdinir was not found to be teratogenic and mutagenic. ^[4]

Cefdinir pharmacokinetics:

· Blood concentration-When six healthy adults take 50, 100, 200 mg (potency) cefdinir orally once on an empty stomach, the peak blood concentration can be reached after about 4 hours, which are 0.64, 1.11 and 1.74 g / ml, respectively. The plasma half-life is 1.6 to 1.8 hours.

Six healthy adults took 100 mg (potency) cefdinir orally once on an empty stomach and after eating. After about 4 hours, the peak plasma concentrations were reached, which were 1.25 and 0.79 g / ml, respectively. After administration with food, its absorption is slightly reduced.
Patients with impaired renal function take 100 mg (potency) of cefdinir orally at a time, and the prolonged plasma half-life is directly proportional to the degree of renal impairment.

After 6 oral hemodialysis patients with 100 mg (titer), the plasma half-life of this product was prolonged by nearly 11 times. In the same patient, 100 mg (titer) cefdinir was taken orally once after a meal, and hemodialysis was performed for 4 hours when the blood concentration reached a peak. The half-life of patients undergoing hemodialysis was shortened, which was about 1/6 of those who did not undergo hemodialysis, and the clearance rate was 61%.

· Distribution: It is distributed in patients' sputum, tonsils, maxillary sinus mucosa, middle ear secretions, skin tissues and oral tissues. It is unknown whether they are distributed in milk.
· Metabolism: No metabolites with antibacterial activity are found in human blood, urine and feces.
Excretion: Cefdinir is excreted mainly through the kidneys.
-When healthy adults (fasting) take oral 50, 100, and 200 mg (potency), the urine excretion rate (0 to 24 hours) is about 26% to 33%, and the peak urine concentration of 4 to 6 hours is 44.3, 81.5, and 132 g / ml.
-Patients with impaired renal function take 100 mg (potency) of cefdinir orally at one time, which is excreted slowly and directly proportional to the degree of renal impairment. ^[4]

Cefdinir Expert Reviews

This product has a broad-spectrum antibacterial activity against Gram-positive and negative aerobic and anaerobic bacteria. Compared with other existing oral cephalosporin antibiotics, this product is effective against Staphylococcus, Streptococcus, Digestive Streptococcus, Propionibacterium Strong antibacterial activity. A clinical trial of 1433 cases (100 mg each time, 3 times a day); the results show that the effective rate of this product for various infections: superficial suppurative disease 89.2%, surgical infection 90%, acute respiratory infection 82.8 %, Chronic respiratory infections 63.1%, urinary tract infections 82.8%, gynecological infections 88.4%, ophthalmological infections 94.3%, and ENT infections 75%. The bacterial clearance rate for Gram-positive bacteria was 91.9%, and the bacterial clearance rate for Gram-negative bacteria was 91.4%. ^[5]