Clarithromycin is an organic compound with chemical formula Cthirty-eightHsixty-nineNOthirteen, a macrolide antibiotic, is a derivative of erythromycin.
It was successfully developed by Japanese Dazheng Company in the early 1990s and registered under the trade name Clarith.Later, Dazheng first transferred its technology to Abbott for production.In 1990, it was listed in Ireland and Italy. In October 1991, it was approved by the FDA as a new IB drug, with the trade name of Biaxin. In 1993, it was listed in Hong Kong, China, as Klacid. In Europe and Asia, it was listed in more than 50 countries around the world, with a steady increase in market usage and played an important role in clinical practice.Clarithromycin and its tablets, currently produced dosage forms include granules, dispersible tablets, sustained release tablets, injections and dry suspensions.
Chemical formula: Cthirty-eightHsixty-nineNOthirteen
Molecular weight: 747.953
CAS No.: 81103-11-9
Physical and chemical properties
Density: 1.18 g/cmthree
Melting point: 217-220 º C
Boiling point: 805.5 º C
Flash point: 440.9 º C
Refractive index: 1.526
Appearance: white or off white crystalline powder
Solubility: Easily soluble in chloroform or acetone, slightly soluble in ethanol, ether or methanol, and almost insoluble in water[1]
Calculate chemical data
Reference value for drainage parameter calculation (XlogP): 3.2
Number of hydrogen bond donors: 4
Number of hydrogen bond receptors: 14
Number of rotatable chemical bonds: 8
Number of tautomers: 3
Topological molecule polar surface area (TPSA): 183
Number of heavy atoms: 52
Surface charge: 0
Complexity: 1190
Number of isotope atoms: 0
Determine the number of atomic structure centers: 18
Number of uncertain atomic structure centers: 0
Determine the number of chemical bond structure centers: 0
Number of uncertain chemical bond structure centers: 0
Number of covalent bond units: 1[1]
purpose
Clarithromycin is a macrolide antibiotic, which is used to treat upper and lower respiratory tract infections, subcutaneous soft tissue infections, etc.
Pharmacopoeia information
Announce
edit
essential information
This product is 6-O-Erythromycin methyl, calculated as anhydrous, containing clarithromycin (Cthirty-eightHsixty-nineNOthirteen）Not less than 94.0%.
character
This product is white or almost white crystalline powder, odorless.
This product is dissolved in acetone or ethyl acetate, slightly soluble in methanol or ethanol, and insoluble in water.
Specific curl
Take this product, weigh it precisely, add chloroform to dissolve it and dilute it quantitatively to make a solution containing about 10mg per 1mL. Determine according to the law (general rule 0621), and the specific rotation is - 99 ° to - 95 °.
identify
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 absorption spectrum of this product should be consistent with that of the control (Spectral Collection 756). If necessary, take an appropriate amount of the test sample and the control sample, dissolve them in chloroform, evaporate to dryness at room temperature, and determine the residue after vacuum drying, which should be consistent with that of the control sample.
inspect
alkalinity
Take this product, prepare a suspension containing 2mg per 1mL with water methanol (19:1) mixed solution, and determine according to the law (general rule 0631), the pH value should be 7.5~10.0.
Crystallinity
Take this product and check it according to law (general rule 0981), and it should meet the requirements.
Related substances
Determine according to the method of high performance liquid chromatography (general rule 0512).
Test solution: Take an appropriate amount of this product, add mobile phase to dissolve and dilute it to make a solution containing about 1.0mg per 1mL.
Control solution: precisely measure 5mL of test solution, place it in a 100mL measuring flask, dilute it with mobile phase to the scale, and shake it well.
Chromatographic conditions: octadecyl silane bonded silica gel is used as filler, phosphate buffer solution (9.11g of potassium dihydrogen phosphate, dissolved with water and diluted to 1000mL, 2mL of triethylamine added, pH adjusted to 5.5 with phosphoric acid) - acetonitrile (600:400) is used as mobile phase, column temperature is 45 ° C, detection wavelength is 210nm, and injection volume is 20 µ L.
System applicability requirements: the trailing factor of clarithromycin peak shall not exceed 2.0, and the resolution between clarithromycin peak and adjacent impurity peak shall meet the requirements.
Determination method: Precisely measure the test solution and the reference solution, respectively inject them into the liquid chromatograph, and record the retention time of the chromatogram to the main component peak 4 times.
Limit: If there is an impurity peak in the chromatogram of the test solution, the area of a single impurity peak shall not be greater than 0.5 times (2.5%) of the main peak area of the reference solution, and the sum of the areas of each impurity peak shall not be greater than 1.2 times (6.0%) of the main peak area of the reference solution.
water content
Take this product, add 10% imidazole anhydrous methanol solution to dissolve it, and determine it according to the moisture determination method (General Rule 0832, Method 1). The moisture content should not exceed 2.0%.
Ignition residue
Take 1.0g of this product and check it according to the law (general rule 0841). The residue should not exceed 0.3%.
heavy metal
Take the residue left under the item of burning residue and check it according to law (the second method of General Rule 0821). The content of heavy metals shall not exceed 20 parts per million.
Assay
Determine according to the method of high performance liquid chromatography (general rule 0512).
Test solution
Take an appropriate amount of this product, weigh it precisely, add mobile phase to dissolve it and dilute it quantitatively to make a solution containing 0.35mg per 1mL.
Reference solution
Take an appropriate amount of clarithromycin reference substance, weigh it precisely, add mobile phase to dissolve it and dilute it quantitatively to prepare a solution containing about 0.35mg per 1mL.
Chromatographic conditions and system suitability requirements
See related substances.
Assay
Accurately measure the test solution and the reference solution, respectively inject them into the liquid chromatograph, and record the chromatogram.Calculate by peak area according to external standard method.
category
Macrolide antibiotics.
Storage
Shading, sealed storage.
preparation
1. Clarithromycin Tablets.
2. Clarithromycin Capsules.
3. Clarithromycin granules.[2]
Brief Introduction to Drugs
Announce
edit
pharmacological action
This product belongs to 14 membered macrolide antibiotics.The antibacterial spectrum is the same as erythromycin, roxithromycin, etc., but the antibacterial effect on gram-positive bacteria such as streptococcus, pneumococcus, staphylococcus is slightly better, and it also has certain antibacterial activity on induced erythromycin resistant strains.Clarithromycin and its metabolites in vivo have enhanced antibacterial activity against influenza bacillus.The product also has certain effect on gonococcus, listeria, campylobacter jejuni, but has stronger effect on legionella pneumophila, mycoplasma pneumonia, chlamydia trachomatis, ureaplasma urealyticum, etc. than erythromycin, and plays a prominent role in new varieties developed in recent years. MICninetyAbout 0.008-0.12mg/L.In addition, it has certain activity to Spirochaeta pallidum, Mycobacterium avium and Toxoplasma muris, and most of them are better than other varieties.In addition to its strong antibacterial effect on anaerobes, its effect on bacteroides fragilis is better than that of erythromycin and other antibiotics. Its after effect on Staphylococcus aureus, Streptococcus pyogenes, and Influenza bacillus is significantly stronger than that of erythromycin.This medicine belongs to macrolide antibiotics. Its mechanism is to inhibit the synthesis of proteins by blocking the binding of 50S subunits of nuclear proteins.This drug has inhibitory effect on gram-positive bacteria such as Staphylococcus aureus, Streptococcus, Pneumococcus, and some gram-negative bacteria such as Haemophilus influenzae, Bacillus pertussis, Diplococcus gonorrhoeae, Legionella pneumophila, and some anaerobic bacteria such as Bacteroides fragilis, Streptococcus digestans, Propionibacterium acnes.In addition, it also has inhibitory effect on mycoplasma.The drug is characterized by similar antibacterial activity to erythromycin in vitro, but stronger antibacterial activity to some bacteria in vivo, such as Staphylococcus aureus, Streptococcus, Haemophilus influenzae, etc.There was cross resistance with erythromycin.
Pharmacokinetics
The product is stable to gastric acid and can be absorbed well after oral administration.The peak concentration was 0.35 μ g/mL at 2h after single dose of 100mg;The peak concentration after oral administration of 1200mg can reach 3.97 μ g/mL.The product can be rapidly distributed to various tissues. The drug concentration in lung tissue reaches 17.5 μ g/g, and the concentration in tonsil, nasal mucosa, and skin is about 2-6 times of the blood concentration in the same period.The ratio of intracellular and extracellular drug concentrations was 16:4.The protein binding rate was 42%~70%.It is mainly excreted through feces and urine.The elimination half reduction period is 2.6~4.4h.There is no need to adjust the dosage for patients with mild renal insufficiency, or elderly people, or patients with mild to moderate hepatic insufficiency.
indication
It is mainly used in the upper and lower respiratory tract caused by sensitive bacteria, including tonsillitis, pharyngitis, sinusitis, bronchitis, pneumonia, skin, soft tissue infection, purulent boil, erysipelas, folliculitis, wound infection, etc., and its efficacy is similar to other macrolides.The product can also be used for genital and urinary infections caused by chlamydia trachomatis or ureaplasma urealyticum, atypical mycobacterial infections in AIDS patients, etc.
Usage and dosage
Adults take 250mg every 12h, and the dose of severe patients can be increased to 500mg every 12h;The course of treatment is generally 7-14 days, depending on the degree of infection.If the creatinine clearance rate is lower than 0.501mL/1.73m2 · s, the dose will be halved.Dose for children: 7.5mg/kg each time, twice a day, and the maximum dose shall not exceed 500mg per day.Mild disease: 250mg each time, severe disease: 500mg each time, once every 12 hours, and the course of treatment is 7-14 days.Children over 12 years old are measured as adults.Children under 12 years old should not use this medicine.
Adverse reactions
1. Nausea, heartburn, abdominal pain, diarrhea and headache can be seen.The temporary elevation of transaminase can be recovered after drug withdrawal.There were cases of biliary hepatitis.Serious infection caused by fungi or drug-resistant bacteria may occur, and the drug should be stopped and treated accordingly.Allergic reactions may occur, with mild cases of drug eruption and urticaria, and severe cases of allergy.There have been reports of transient side effects of the central nervous system, such as anxiety, dizziness, insomnia, hallucinations, nightmares and blurred consciousness.Adverse reactions included diarrhea (3%), nausea (3%), taste change (3%), dyspepsia (2%), abdominal pain or discomfort (2%), and headache (2%), which were generally mild.
2. ALT, AST, LDH, alkaline phosphatase and bilirubin increased (all<1%);Leukopenia (<1%), prolonged prothrombin time (1%), increased BUN (4%), and increased serum creatinine (<1%).
contraindication
People who are allergic to macrolides, pregnant women, lactating women, people with severe liver and kidney dysfunction, arrhythmia, bradycardia,Q-TThe drug is mainly metabolized and excreted in the liver, so the patients with liver dysfunction, severe renal dysfunction and the elderly over 65 years old should pay special attention to the adverse reactions when taking the drug.Gastrointestinal dysfunction and systemic symptoms may occur when overdose is taken, and gastric lavage and supportive therapy may be given.Neither hemodialysis nor peritoneal dialysis can remove the product, so it is necessary to eliminate the drugs that have not been absorbed (such as gastric lavage) as soon as possible and give symptomatic treatment.It is forbidden for pregnant women (the concentration of this product in animal embryos is 2~17 times that of human serum).Breastfeeding women should use it with caution (it is advisable to stop breastfeeding).
Overdose
When taking large doses of clarithromycin, there may be gastrointestinal discomfort.Symptoms caused by excess should be promptly washed stomach and given appropriate supportive treatment.So far, no blood or peritoneal dialysis has been reported to clear clarithromycin.However, it is necessary to eliminate the unabsorbed drugs as soon as possible and take appropriate symptomatic treatment.
Drug interaction
This product can interfere with the metabolism of carbamazepine, making the blood concentration of the latter significantly increased. When the two are used together, the blood concentration should be monitored, and the dosage should be adjusted if necessary.The combination of theophylline and theophylline can increase the blood concentration of theophylline, but it is generally unnecessary to adjust the dosage of theophylline.This product can change the blood concentration of the following drugs used in combination: digoxin (rise), theophylline (rise), oral anticoagulant (rise), ergotamine or dihydroergotamine (rise), triazolam (rise) and show stronger effect.For carbamazepine, cyclosporine, hexbarbital, phenytoin, etc., it can also block metabolism and strengthen the effect.
security information
Announce
edit
Safety terminology
S26：In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
After eye contact, immediately flush with plenty of water and seek medical advice.
