What Are the Different Erythromycin Interactions?

Erythromycin, clinically mainly used in patients with tonsillitis, scarlet fever, diphtheria and carrier, streptococcus pneumoniae, lower respiratory tract infection caused by streptococcus Pneumonia, this product can be used as the drug of choice. It can also be applied to upper respiratory tract infections caused by influenza bacilli, staphylococcus aureus skin and soft tissue infections, syphilis, intestinal amoebiasis, etc.

Drug type: Essential medicines
Drug name: Erythromycin

English name: Erythromycin
Chinese alias: Erythromycin; edemis; adriamycin
English alias: Ilotycin; Erythrocin; Ermycin

Introduction to erythromycin compounds

Erythromycin Basic Information

Chinese name: erythromycin

Chinese alias: Erythromycin base; Edimicin; Fu Aili; Erythromycin; Erythromycin base; Adammycin; Weimycin; Xinhongkang

Chemical name: 5- (4-dimethylamine tetrahydro-3-hydroxy-6-methyl-2-pyranyloxy) -6,11,12,13-tetrahydroxy-2,4,6,8, 1o, 12-hexamethyl-9-oxo-3- (tetrahydro-5-hydroxy-4-methoxy-4,6-dimethyl-2-pyranoxy) pentadecanoic acid- -Lactone

English name: Erythromycin

English alias: Ergel; USP; EES; erycin; ERYC; Eritomicina; Ermycin; Eryc; Erythromycin Base; Erythromycinum; Paedlathrocin

Molecular structure formula:

CAS number: 114-07-8

Molecular formula: C ₃₇ H ₆₇ NO ₁₃

Molecular weight: 733.92700

Exact mass: 733.46100

PSA: 193.91000

LogP: 1.78560

Erythromycin physical and chemical properties

Appearance and properties: soft colorless powder

Density: 1.2g / cm ³

Melting point: 138-140ºC

Boiling point: 818.4ºC at 760mmHg

Flash point: 448.8ºC

Stability: stable under normal temperature and pressure

Storage conditions: 0-6ºC

Vapor pressure: 4.94E-31mmHg at 25 ° C

This product is a macrolide antibiotic, made from Streptomyces erythreus culture medium isolated from the soil on the island of Fibon Panay. It was first published by EliLilly in 1952. Several analogues such as erythromycin B and C are produced in the culture medium at the same time, and the differences in the solubility of the solvents are used to remove them. This product is white or light yellow white crystalline powder, odorless, bitter taste, hygroscopicity in the air, easily soluble in ethanol, chloroform, acetone and ether, etc., slightly soluble in water. Solubility increases after salt formation. It is relatively stable in a dry state, and the aqueous solution is more stable under refrigeration, and the titer gradually decreases at room temperature. It is unstable in the presence of acid, is more stable in slightly alkaline, and has a significantly lower titer below pH4. MP 135-140 ° C (decomposed), specific rotation -70-78 ° (2%, ethanol solution).

Erythromycin Safety Information

Customs Code: 2941500000

WGK Germany: 2

Danger category code: R42 / 43

Safety instructions: S24-S37-S45

Dangerous goods sign: Xn

Erythromycin production method

This product is an alkaline antibiotic extracted from the culture fluid of Streptomyces erythreus. During purification, using its characteristics of dissolving in different solvents in different pH, repeated extraction with butyl acetate and aqueous solution to achieve the purpose of concentration and purification, and finally freeze-crystallization in butyl acetate solution to obtain erythromycin base.

Erythromycin use

This product is a macrolide antibiotic with an antibacterial spectrum similar to that of penicillin. It is effective against Gram-positive bacteria such as Staphylococcus, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus faecalis, Streptococcus hemolyticus, Clostridium Bacillus, diphtheria and anthracnose have strong inhibitory effects. It also has a certain inhibitory effect on Gram-negative bacteria such as Neisseria gonorrhoeae, Helicobacter, Pertussis, Brucella, Legionella, Meningococcus, and Haemophilus influenzae, Bacteroides, some dysentery, and E. coli. In addition, it has inhibitory effects on Mycoplasma, Actinomyces, Borrelia, Rickettsia, Chlamydia, Nocardia, Mycobacterium and Amoeba. Staphylococcus and other Streptococcus bacteria such as Staphylococcus are easily resistant to this product. It is characterized by strains that are resistant to penicillin and sensitive to this product. The mechanism of action is mainly combined with the 50S subunit of ribonucleoproteins, which inhibits peptide acyltransferase, affects the process of ribonucleoprotein translocation, hinders peptide chain growth, inhibits bacterial protein synthesis, and is a bacteriostatic agent ^[1] .

Erythromycin Pharmacopoeia Standard

[Identification] (1) In the chromatogram recorded under the erythromycin A component, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the standard solution. (2) The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 167). If it is not consistent, take an appropriate amount of this product and the standard product, add a small amount of chloroform to dissolve, evaporate to dryness in a water bath, and place it in a phosphorus pentoxide dryer to measure it under reduced pressure. Except for the wavelength range of 1980cm-1 to 2050cm-1, Consistent with the map of the control.

an examination

Alkalinity

Take 0.1g of this product, add 150ml of water, shake, and determine according to law (Appendix VI H). The pH value should be 8.0 ~ 10.5.

Erythromycin B, C components and related substances

Take this product, dissolve and dilute it with phosphate buffer solution (pH7.0) -methanol (15: 1) to make a solution containing about 4mg per 1ml as the test solution; take 5ml precisely and place it in a 100ml measuring bottle In the process, it was diluted to the mark with phosphate buffer (pH 7.0) -methanol (15: 1), and shaken as the control solution. According to the chromatographic conditions under the erythromycin A component, take 20 l of the reference solution and inject it into the liquid chromatograph, adjust the detection sensitivity, so that the peak height of the main component chromatographic peak is about 50% of the full range, and the test solution is accurately measured. 20 l each with the control solution were injected into the liquid chromatograph, and the chromatogram was recorded to 3.5 times the peak retention time of the main component. Erythromycin B is calculated based on the corrected peak area (multiplied by the correction factor 0.7) and the erythromycin C peak area must not be greater than the main solution area of the control solution (5.0%). If there are impurity peaks in the chromatogram of the test solution, the erythromycin enol ether and impurity 1 are calculated based on the corrected peak areas (respectively multiplied by the correction factors of 0.09 and 0.15) and the peak areas of other single impurities should not be larger than the main peak of the control solution. 0.6 times the area (3.0%); the sum of the peak areas of other impurities must not be greater than the area of the main peak of the control solution (5.0%). Any peaks smaller than 0.01 times the area of the main peak of the control solution in the chromatogram of the test solution can be ignored.

Thiocyanate

Take this product about O.lg, weigh it accurately, put it in a 50ml brown bottle, add 20ml of methanol to dissolve, add 1ml of ferric chloride test solution, dilute to the mark with methanol, shake well, and use it as the test solution; take 105 2 parts of potassium thiocyanate dried at ° C for 1 hour, each about 0.lg, accurately weighed, put into two 50ml measuring flasks respectively, add 20ml of methanol to dissolve and dilute to the mark, shake well, take 5ml precisely, place In a 50ml volumetric flask, dilute to the mark with methanol, shake well, and then accurately measure 5ml, place in a 50ml brown bottle, add 1ml of ferric chloride test solution, dilute to the mark with methanol, shake well, and use as a reference solution; Take 1ml of ferric chloride test solution, place it in a 50ml brown bottle, and dilute to the mark with methanol as a blank solution. According to the ultraviolet-visible spectrophotometry (Appendix IV A), the absorbance was measured at a wavelength of 492 nm (the test solution, the reference solution and the blank solution should be measured within 30 minutes). The ratio should be 0.985 to 1.015. The content of thiocyanate in erythromycin must not exceed 0.3%. The molecular weights of thiocyanate and potassium thiocyanate are 58.08 and 97.18, respectively.

Moisture

Take about 0.2g of this product, add 10% imidazole anhydrous methanol solution to dissolve, and measure according to the moisture measurement method (Appendix M first method A), the moisture content should not exceed 6.0%.

Residue on ignition

Must not exceed 0.2% (Appendix N).

Erythromycin A component

Determined by high performance liquid chromatography (Appendix VD).

1. Chromatographic conditions and system suitability tests

Use octadecylsilane bonded silica as a filler; take a phosphate solution (take 8.7 g of dipotassium hydrogen phosphate, add 1000 ml of water, adjust the pH to 8.2 with phosphoric acid)-acetonitrile (40:60) as the mobile phase; the flow rate is 0.8 ~ 1.0ml per minute; column temperature is 35 ° C; wavelength is 215nm, take appropriate amount of erythromycin standard, heat to destroy at 130 ° C for 4 hours, dissolve with an appropriate amount of methanol (10mg plus 1ml of methanol), and dissolve with phosphate buffer (PH 7.0) -methanol (15: 1) was diluted to make a solution containing about 4 mg per ml, and 20 l was taken and injected into a liquid chromatograph. Record the chromatogram to 5 times the retention time of erythromycin A. Peaks in the order of erythromycin C, erythromycin A, impurity 1, erythromycin B, erythromycin enol ether (if necessary, use erythromycin C erythromycin B erythromycin enol ether control Product for peak positioning). The resolution of the erythromycin A peak and the erythromycin enol ether peak should be greater than 14.0, and the tailing factor of the erythromycin A peak should be less than 2.0.

2. Assay

Take about 0.1 lg of this product and erythromycin standard, accurately weigh, add 5ml of methanol to dissolve, and quantitatively dilute with phosphate buffer solution (pH7.0) -methanol (15: 1) to make about The solution containing 4mg was used as the test solution and the standard solution respectively. The Mpl of the test solution and the standard solution were precisely measured and injected into the liquid chromatograph respectively. The chromatogram was recorded and the peak area was calculated according to the external standard method. Content of erythromycin A in the test product. Calculated as anhydrous, it shall not be less than 88.0%.

[Content determination] Precisely weigh the proper amount of this product, dissolve it with ethanol (10mg plus 1ml of ethanol), and make a solution containing about 1,000 units per ml with sterilized water. Method or turbidity method), the confidence limit rate shall not be greater than 7%. 1000 erythromycin units correspond to 1 mg of C37H67N013.

[Category] Macrolide antibiotics.

[Storage] Sealed and stored in a dry place.

Erythromycin Drug Description

Erythromycin pharmacological action

Erythromycin erythromycin is a basic antibiotic produced by Streptomyces erythreus and belongs to the class of macrolides. Erythromycin is a bacteriostatic agent, but it also has a bactericidal effect on highly sensitive bacteria at high concentrations. Its mechanism of action is that it can penetrate the bacterial cell membrane and reversibly bind to the 50S subunit of the bacterial ribosome near the donor site ("P" position), blocking the transfer of ribonucleic acid (tRNA) to the "P" position, and also Blocking the displacement of the polypeptide chain from the accepting position ("A" position) to the "P" position, the bacterial protein synthesis is inhibited, thereby playing an antibacterial effect. Erythromycin is only effective against actively dividing bacteria. Erythromycin has a broad antibacterial spectrum and is effective against most Gram-positive bacteria, some Gram-negative bacteria and some atypical pathogenic bacteria. Erythromycin against Staphylococcus (including enzyme-producing strains), groups of Streptococcus, pneumococcus, anthracnose, clostridium tetanus, diphtheria, gonococcus, meningococcus, influenza, pertussis, campylobacter Genus, Legionella, Listeria, Isreal actinomycetes have strong antibacterial activity; it also has a good inhibitory effect on Treponema pallidum, Mycoplasma pneumoniae, Leptospira, Rickettsia; Chlamydia. Erythromycin lactobionate is the lactobionate of erythromycin. After absorption of erythromycin lactobionate, the active ingredient erythromycin is released by hydrolysis. Erythromycin can penetrate the bacterial cell membrane and reversibly bind to the bacterial ribosome near the donor site ("P" site), blocking the transfer of ribonucleic acid (tRNA) to the "P" site, and also blocking the polypeptide chain The displacement from the accepting position ("A" position) to the "P" position inhibits the protein synthesis of bacterial cells, thereby acting as an antibacterial effect. Erythromycin lactobionate is effective against most Gram-positive bacteria, some Gram-negative bacteria, and some atypical pathogenic bacteria. Erythromycin against Staphylococcus (including enzyme-producing strains), groups of Streptococcus, pneumococcus, anthracnose, clostridium tetanus, diphtheria, gonococcus, meningococcus, influenza, pertussis, Campylobacter jejuni Genus, Legionella, Listeria, Isreal actinomycete have strong antibacterial activity; also have good inhibitory effect on Treponema pallidum, Mycoplasma pneumoniae, Leptospira, Rickettsia, Chlamydia, etc.

Erythromycin pharmacokinetics

Erythromycin erythromycin is 200-250 mg orally, and the blood concentration reaches a peak value after 2 to 3 hours, generally lower than 1 g / ml. Except for cerebrospinal fluid and brain tissues after drug absorption, they are widely distributed in various tissues and body fluids, especially in liver, bile and spleen, which have higher concentrations (the concentration in bile can reach 10 to 40 times the blood concentration). The concentration of the drug in kidney, lung and other tissues can be several times higher than the concentration of bleeding drug; it is also higher in the subcutaneous tissue, sputum and bronchial secretions (the concentration in sputum is similar to the blood concentration); 2. The concentration in pus can reach the effective bacteriostatic concentration. Erythromycin can enter the prostate and seminal vesicles in a certain amount (about 33% of the blood concentration), but it is not easy to penetrate the blood-cerebrospinal fluid barrier. When the meningitis is inflamed, the concentration in the cerebrospinal fluid is only about 10% of the blood concentration. Erythromycin can enter the fetal blood circulation and breast milk, the fetal blood concentration is 5% to 20% of the maternal blood concentration, and the breast milk can reach more than 50% of the blood drug concentration. After oral administration of different salts of erythromycin, the bioavailability is about 30% to 65%. The apparent distribution volume is 0.9L / kg. The protein binding rate is 70% to 90%. The half-life is about 1.4 to 2.0 hours, and the half-life of patients with anuria can be extended to 4.8 to 6.0 hours. Free erythromycin is metabolized in the liver, mainly concentrated in the liver and excreted from the bile. About 2% to 5% of the oral amount and 10% to 15% of the injected amount are excreted from the glomerulus and excreted in the urine. The concentration in urine can reach 10 100g / ml. In addition, the stool also contains a certain amount of drugs. Peritoneal dialysis and hemodialysis are not effective in removing erythromycin. Erythromycin lactobionate is a water-soluble erythromycin lacturonic acid ester, which reaches its peak plasma concentration after intravenous infusion. Intravenous infusion of 2 g within 24 hours, the average blood concentration was 2.3 to 6.8 mg / L. Except for cerebrospinal fluid and brain tissues after drug absorption, they are widely distributed in various tissues and body fluids, especially in liver, bile and spleen with higher concentrations. The concentration of the drug in kidney, lung and other tissues can be several times higher than the concentration of bleeding drug; it is also higher in the subcutaneous tissue, sputum and bronchial secretions (the concentration in sputum is similar to the blood concentration); 2. The concentration in pus can reach the effective bacteriostatic concentration. Erythromycin can enter fetal blood circulation and breast milk, but does not easily penetrate the blood-cerebrospinal fluid barrier. Free erythromycin is mainly metabolized in the liver, concentrated in the liver, excreted with bile, and undergoes enterohepatic circulation. About 10% to 15% of the injection volume is excreted from the glomerulus and excreted in the urine. The concentration in urine can reach 10 ~ 100mg / L. In addition, the stool also contains a certain amount of drugs. Peritoneal dialysis and hemodialysis are not effective in removing erythromycin.

Erythromycin indication

Erythromycin erythromycin can be used clinically as the drug of choice for the following infections:

1. Acute tonsillitis, acute pharyngitis, and sinusitis caused by hemolytic streptococcus and pneumococcus.

2. Scarlet fever and cellulitis caused by hemolytic streptococcus.

3. Mycoplasma pneumoniae pneumonia, Chlamydia pneumoniae pneumonia.

4. Gas gangrene, anthrax, and tetanus.

5. Diphtheria (adjuvant treatment) and diphtheria carriers.

6. Chlamydia trachomatis conjunctivitis.

7. Urogenital infections caused by Chlamydia and Mycoplasma.

8. Listeriosis.

9. Legionella pneumonia (Legionella pneumoniae).

10. Neisseria gonorrhoeae infection.

11. Campylobacter jejuni enteritis.

12. Oral infections caused by anaerobic bacteria.

13. Whooping cough.

14. Actinomycosis.

15. Dermatology is mainly used for non-gonococcal urethritis (cervicitis), gonorrhea, syphilis, soft chancre, chlamydia lymphogranuloma (STD lymphogranuloma), acne and Staphylococcus aureus skin infection, scarlet fever, etc.

Erythromycin Contraindications

Erythromycin can pass through the placental barrier and enter breast milk. Pregnant women and nursing women should use it with caution. People who are allergic to macrolides.

Erythromycin dosage

1. (1) Commonly used oral dose: 1 to 2 g daily, divided into 3 to 4 times. Legionnaires' disease: the daily dose can be increased to 2 ~ 4g, divided into 4 times. (2) Local administration: For trachoma, conjunctivitis, keratitis, apply an appropriate amount of eye ointment to the eyelid several times a day. (3) Dose at renal insufficiency: Patients with renal insufficiency generally do not need to reduce the dosage.

2. Children: (1) Oral administration: 30-50 mg / kg daily, divided into 3 to 4 times. (2) Local administration: Trachoma, conjunctivitis, keratitis, apply an appropriate amount of eye ointment to the eyelid several times a day.

3. Intravenous infusion: (1) Adults: General dosage: 1 to 2 g per day, divided into 2 to 4 times. Legionnaires' disease: 3 to 4 g per day, divided into 4 doses. The high dose cannot exceed 4g. (2) Children: Administer 20 to 40 mg / kg daily in 2 to 4 doses.

Erythromycin adverse reactions

1. Gastrointestinal symptoms such as diarrhea, nausea, vomiting, middle and upper abdominal pain, and loss of appetite may occur after administration. The incidence is related to the size of the dose.

2. Hepatic toxicity such as fatigue, jaundice, and abnormal liver function may occur even after administration.

3. Large doses (4g per day) may cause ototoxicity after administration to patients with liver and kidney disease and elderly patients. Mainly manifested as hearing loss. It may be related to the high blood concentration (> 12mg / L), and most of them can return to normal after stopping the drug.

4. After taking the drug, allergic reactions such as drug fever, rash, and eosinophilia may occur, and the incidence is about 0.5% to 1%.

5. A small number of patients occasionally have arrhythmias, oral or vaginal candidiasis, etc.

6. In some patients, intravenous irritation or phlebitis may occur after intravenous administration.

Erythromycin precautions

(1) Erythromycin is a bacteriostatic drug. Administration should be carried out at certain intervals to maintain the concentration of the drug in the body and facilitate the function. (2) Erythromycin tablets should be swallowed whole. If taking medicine powder, it will be destroyed by gastric acid and its effect will be reduced. Toddlers can take acid stabilized erythromycin. (3) Intravenous infusion is likely to cause phlebitis, and the infusion rate should be slow. (4) Erythromycin destroys and degrades in acidic infusion, and generally should not be compatible with low pH glucose infusion. In 500ml of 5% to 10% glucose infusion, add vitamin C injection (sodium ascorbate 1g) or 0.5ml of 5% sodium bicarbonate injection to raise the pH to more than 5, and then add erythromycin lactate. Helps stabilize.

Erythromycin drug interaction

1. Erythromycin is used in combination with antiepileptic drugs such as carbamazepine and valproic acid, which can inhibit the metabolism of carbamazepine and valproic acid, resulting in the latter's blood concentration rising and toxic reactions. And carbamazepine can reduce erythromycin efficacy through liver microsomal oxidase.

2. The combination of erythromycin and cyclosporine can promote the absorption of cyclosporine and interfere with its metabolism. The clinical manifestations are abdominal pain, hypertension and liver dysfunction.

3. Erythromycin used together with xanthines (except dihydroxypropphylline) can reduce liver clearance of aminophylline, resulting in increased serum aminophylline concentration and / or increased toxic response. This phenomenon is more likely to occur after 6 days of simultaneous use, and the reduction in aminophylline clearance is proportional to the peak of erythromycin serum.

4. The combination of erythromycin and digoxin can clear the intestinal flora that can inactivate digoxin, which leads to the enterohepatic circulation of digoxin, which causes the blood concentration of digoxin to rise and cause toxic reactions.

5. Erythromycin combined with lovastatin can inhibit the metabolism of lovastatin and increase its plasma concentration, which may cause rhabdomyolysis.

6. Erythromycin combined with midazolam and triazolam can reduce the clearance of midazolam and triazolam and enhance its effect.

7. The combination of erythromycin and alfentanil can inhibit the metabolism of alfentanil and prolong its action time.

8. Combination of erythromycin with other liver toxicity drugs may enhance liver toxicity.

9. High-dose erythromycin combined with ototoxic drugs may increase ototoxicity; patients with impaired renal function are particularly prone to occur.

10. Erythromycin in combination with antihistamines such as astemizole and terfenadine can increase cardiac toxicity and cause arrhythmia.

11. Combination of erythromycin and ergotamine tartrate can cause acute ergot poisoning (such as peripheral vasospasm).

12. Long-term use of erythromycin in patients taking warfarin can lead to prolonged prothrombin time, thereby increasing the risk of bleeding.

13. Erythromycin is used in combination with chloramphenicol and lincomycin and has an antagonistic effect.

14. The combination of erythromycin and -lactam can reduce the antibacterial activity of both.

15. Erythromycin is taken with the contraceptive pill, which can block the enterohepatic circulation of sex hormones and reduce the effectiveness of the contraceptive pill.

Erythromycin poisoning

The erythromycin antibacterial spectrum is similar to penicillin, and it has a strong inhibitory effect on gram-positive bacteria and a considerable inhibitory effect on gram-negative bacteria. A few Mycobacteria and Amoeba have inhibitory effects. Often an alternative to penicillin allergy. The oral absorption is poor, ranging from 18% to 45%, the plasma protein binding rate is 73%, the half-life is 1.5h, and it can be extended to 6h when there is no urine. Adults usually take 1 to 2 g / d in 3 to 4 doses. It can also be made into eye ointment to treat trachoma, conjunctivitis and keratitis, and apply it to the eyelid.

Clinical manifestation

1. Common adverse reactions are gastrointestinal reactions, nausea, vomiting, stomach pain, diarrhea, mouth pain, and loss of appetite. Incidence is dose-dependent. Can induce pseudomembranous enteritis.

2. Allergic reactions: various rashes, drug fever, and eosinophilia. One case reported allergic purpura and renal failure. Esterified erythromycin can cause bile accumulation liver damage.

3. Application of large doses of erythromycin can occasionally cause tinnitus and temporary hearing impairment.

4. Intravenous infusion medication can easily cause phlebitis.

5. It has been reported that one case of myasthenia gravis occurred after 1.5 g of the drug, and disappeared after stopping the drug.

treatment

The main points of treatment for erythromycin poisoning are:

1. Discontinue the drug when toxic reaction occurs, and intravenous fluid replacement promotes excretion.

2. When severe jaundice occurs, glucocorticoid therapy is given.

3. When allergic reactions occur, anti-allergic treatment should be given ^[2] .

Erythromycin preparation

Enteric (tablets, capsules), (ethyl succinate) tablets, capsules: 0.125g (125,000 units), 0.25g (250,000 units) sterile powder for injection: 0.25g (250,000 units), 0.3 g (300,000 units) eye ointment: 0.5% ointment: 1%

Erythromycin expert review

Erythromycin is the drug of choice for Legionella infection, Enterobacter coli, enteritis, Mycoplasma pneumonia, infant pneumonia caused by Chlamydia trachomatis and conjunctivitis, and urinary system infection caused by Chlamydia. It also has good effects on anthrax, gas gangrene, syphilis, non-tuberculous mycobacterial infections, Q fever, actinomycosis, and acne. In recent years, erythromycin has become a widely-resistant antibiotic for Mycoplasma, and some data show that its drug resistance is as high as 27.7%. Therefore, drug sensitivity tests are an important basis for guiding the clinical application of antibiotics to treat Mycoplasma urinary tract infection. Erythromycin is easily soluble in water and can be made into intravenous preparations. It is often used in patients who cannot tolerate oral erythromycin or have severe infections. Erythromycin has a strong inhibitory effect on Propionibacterium acnes, and also inhibits Gram-negative bacteria such as Neisseria gonorrhoeae, Chlamydia, Mycoplasma, etc. It is mainly used to treat acne and purulent skin diseases and can effectively reduce the number of Acne bacteria .

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