Amoxicillin is a national essential drug.
2 common name amoxicillin.
3 English name amoxicillin
4 Amorim, another name for powerful Amorim; One morning; Amoxicillin; Amoxicillin; An Fuxi; Onasin; Fentazillin; Edelweiss; Netami; A strong forest; Amoxicillin; Amoxicillin; Terex; Novoda Benin; Amoxicillin
Classification of Antibacterials >: β -lactam antibiotics? & gt Penicillins >:? Semi-synthetic penicillins
6 Amoxicillin has strong pharmacological action. Amoxicillin has good antibacterial activity against Streptococcus pneumoniae and Streptococcus hemolyticus, aerobic gram-positive cocci such as Staphylococcus aureus and Enterococcus faecalis, and aerobic gram-negative bacteria such as Escherichia coli, Proteus mirabilis, Salmonella, Haemophilus influenzae, Neisseria gonorrhoeae and Helicobacter pylori. The antibacterial spectrum is the same as that of ampicillin, but it has strong acid resistance and bactericidal effect. Amoxicillin and ampicillin have complete cross-resistance. [ 1]
The acid resistance of amoxicillin is stronger than that of ampicillin (the blood concentration of amoxicillin is twice as high as that of ampicillin by taking the same amount of drugs orally). Its bactericidal effect is better than ampicillin, especially for some streptococcus and salmonella.
Amoxicillin is effective for gram-positive bacteria sensitive to penicillin. It has strong antibacterial activity against gram-negative bacteria that do not produce enzymes, such as Haemophilus influenzae, Escherichia coli, Proteus mirabilis, Salmonella, Shigella dysenteriae, Neisseria meningitidis and Neisseria gonorrhoeae. It has certain antibacterial activity against some Escherichia coli, Legionella and Campylobacter fetus. In addition, it also has a good curative effect on leptospira and Treponema pallidum. Most Shigella, most Enterobacteriaceae, Bacteroides fragilis and Pseudomonas aeruginosa are resistant to amoxicillin.
7 Pharmacokinetics Amoxicillin is absorbed rapidly after oral administration, 75% ~ 90% can be absorbed through gastrointestinal tract, and the peak time is about 2 hours. Widely distributed, the apparent distribution volume is 0.4 1L/kg, and the plasma protein binding rate is 17% ~ 20%. It can penetrate the placenta, and its concentration in umbilical cord blood is 1/4 ~ 1/3 of maternal blood concentration. The concentration of drugs in milk, sweat and tears is extremely low. [ 1]
The elimination half-life is 1 ~ 1.3 hours; The half-life of patients with severe renal insufficiency can be extended to about 7 hours. After a single oral administration of 0.25g and 0.5g, 24% and 33% of the doses were metabolized in the liver [1] respectively.
About 60% of the oral dose is excreted with feces through the kidney within 6 hours. 20% of the oral dose is excreted with penicillic acid in urine; Other drugs can be excreted through bile. Hemodialysis can remove some drugs, but peritoneal dialysis can't remove amoxicillin. [ 1]
After oral administration of 0.25, 0.5 and 1g, the peak plasma concentration was 5. 1, 10.8 and 20.6μg/ml, respectively, and the peak time was about 2 hours.
The peak blood concentration of 500mg amoxicillin sodium by intramuscular injection was 65438 04μ g/ml, which was similar to the peak blood concentration of the same dose by oral administration, and the peak time was about 65438±0h.
After intravenous injection of 500mg amoxicillin sodium, the blood concentration was 42.6μg/ml after 5 minutes and 65,438 0 μ g/ml after 5 hours.
The drug is widely distributed after absorption, and the distribution volume is 0.4 1L/kg.
Amoxicillin can permeate the placenta, and its concentration in umbilical cord blood is 1/4 ~ 1/3 of that in maternal blood. The concentration of drugs in milk, sweat and tears is extremely low.
The authors of acute pneumonia or chronic bronchitis took amoxicillin 500mg orally. After 2 ~ 3 or 6 hours, the average drug concentration in sputum was 0.52μg/ml and 0.53μg/ml respectively, and the blood drug concentration in the same period was 1 1μg/ml and 3.5μg/ml respectively.
After oral administration of 1g and1~ 2 hours in children with chronic otitis media, the drug concentration in middle ear fluid was 6.2μg/ml.
Patients with tuberculous meningitis take 1.0g orally. After 2 hours, the drug concentration in cerebrospinal fluid was 0. 1 ~ 1.5μ g/ml, which was equivalent to 0.9% ~ 2 1. 1% of the blood drug concentration in the same period. After intravenous injection of 2g 1.5h, the drug concentration in cerebrospinal fluid reached 2.9 ~ 40.0μ g/ml, which was about 8% ~ 93% of the blood drug concentration.
The drug concentration in urine is very high, and the drug concentration in urine is as high as 0.3 ~ 1.3 mg/ml after oral administration of 250mg.
The binding rate of amoxicillin is 17% ~ 20%, and the half-life is 1.0 ~ 1.3h, which can be extended to 5 ~ 20h in patients with severe renal insufficiency.
Indications: Li Qiang amoxicillin is used for respiratory tract, urinary tract and biliary tract infections caused by sensitive bacteria, typhoid fever and leptospirosis. Combined clarithromycin and omeprazole (or other proton pump inhibitors) can be used to eradicate Helicobacter pylori in stomach and duodenum. [ 1]
1. Typhoid fever, other salmonella infections and typhoid fever carriers.
2. Lower urinary tract infection caused by sensitive bacteria, nongonococcal urethritis, nonspecific urethritis (cervicitis), etc.
3. Ear, nose, throat, respiratory tract and soft tissue infections caused by Streptococcus pneumoniae, Staphylococcus aureus which does not produce penicillin, Streptococcus hemolyticus and Influenza Bacillus.
4. Leptospirosis.
9 contraindications are forbidden for people who are allergic to amoxicillin or other penicillins [1].
Patients with infectious mononucleosis, cytomegalovirus infection, lymphocytic leukemia and lymphoma are prone to rash and should be avoided. [ 1]
10 precautions are the same as those of penicillin drugs. Food can delay the absorption of amoxicillin, but it does not affect the total absorption of drugs. In order to reduce gastrointestinal reaction, it should be taken after meals. [ 1]
1 1 Adverse reactions The adverse reactions of amoxicillin are the same as those of other penicillins. Gastrointestinal reactions are common after oral administration, such as nausea, vomiting, diarrhea, and occasionally pseudomembranous enteritis. [ 1]
The common allergic reactions of penicillin include severe anaphylactic shock and serum sickness type reaction, leukopenia, drug eruption, contact dermatitis and asthma attack. Toxic reactions of low-dose drugs are rare. Peripheral neuritis can occur at the site of intramuscular injection. Intrathecal injection of more than 20,000 units or large-dose intravenous drip can cause convulsion, muscle clonus and lethargy, and can also cause temporary mental disorder, which can be recovered by stopping the drug or reducing the dose. Long-term drug use causes double infection, and penicillin-resistant staphylococcus aureus, gram-negative bacilli or candida infection may occur. [2]
The total incidence of adverse reactions in clinical application of amoxicillin is 5% ~ 6%, and about 2% patients need to stop taking the drug.
1. Diarrhea, nausea, vomiting and other gastrointestinal symptoms are common, accounting for about 3. 1%.
2. Symptoms of allergic reactions such as rash, drug fever and asthma are also common. It is particularly prone to infectious mononucleosis.
3. A few patients occasionally cause hepatorenal toxicity (abnormal liver function, acute interstitial nephritis, etc.). ).
4. A few patients occasionally have eosinophilia and leukopenia after taking the medicine.
5. Long-term high-dose medication can cause flora imbalance and double infection of candida or drug-resistant bacteria.
12 dosage form specifications tablets, capsules, granules and dry suspensions: ① 0.125g; ② 0.25g. [1].
13 the usage and dosage of amoxicillin are taken orally [1].
(1) Adult: 0.5g once, every 6-8 hours 1 time. The daily dose should not exceed 4g. Creatinine clearance rate 10 ~ 30ml/min, 0.25~0.5g once, every 1 2h1time; The creatinine clearance rate is less than 10ml/min, 0.25~0.5g once every 24 hours 1 time. [ 1]
(2) Children: ① Children over 3 months: 25 ~ 50mg/kg daily, every 8 hours 1 time. ② Infants under 3 months old: 30mg/kg daily, every 12 hours 1 time. [ 1]
14 drug interaction (l) Combined with probenecid, aspirin, indomethacin and sulfonamides, it can reduce the excretion of amoxicillin, prolong the half-life and increase the blood drug concentration [1].
Probenecid can delay the renal excretion of amoxicillin and increase the blood concentration.
(2) Combined with allopurine uric acid synthesis inhibitor, the risk of skin adverse reactions increases [1].
Allopurinol can increase the incidence of skin and mucosal adverse reactions of amoxicillin.
(3) Combination with methotrexate can increase the toxicity of methotrexate [1].
Amoxicillin can reduce the renal clearance rate of methotrexate, thus increasing the toxicity of methotrexate.
(4) Taking contraceptives at the same time may affect the contraceptive effect [1].
When amoxicillin is combined with contraceptives, it can metabolize estrogen or reduce its intestinal and hepatic circulation, thus reducing the efficacy of oral contraceptives.
(5) When combined with β -lactamase inhibitors such as clavulanic acid, the antibacterial effect is obviously enhanced. Clavulanic acid can not only enhance the sensitivity of β -lactamase producing strains to amoxicillin, but also enhance the effect of amoxicillin on some insensitive strains, including Bacteroides, Legionella, Nocardia and Pseudoankle.
(6) Amoxicillin can weaken the immune response of live typhoid vaccine, and its possible mechanism is that Amoxicillin has antibacterial activity against Salmonella typhi.
Clinical application of 15 amoxicillin It is reported that amoxicillin can achieve satisfactory curative effect in the treatment of typhoid fever, other salmonella infections and typhoid fever carriers, and its clinical effect, bacteriological clearance rate and body temperature reaction are better than chloramphenicol. Satisfactory results can also be achieved in the treatment of urinary tract infection caused by sensitive bacteria. For patients whose infection is confined to the lower urinary tract, a single dose of 3g can achieve satisfactory results. Amoxicillin can be used for infections of five senses, skin and soft tissues caused by pneumococcus, Staphylococcus aureus which does not produce penicillin, hemolytic streptococcus and influenza bacillus. It can be used in combination with H2 receptor antagonist or proton pump inhibitor to treat gastritis and duodenal ampulla ulcer caused by Helicobacter pylori.
16 amoxicillin is used to treat typhoid fever, other salmonella infections, urinary tract infections caused by typhoid carriers and sensitive bacteria, and leptospirosis caused by pneumococcus, Staphylococcus aureus, hemolytic streptococcus and influenza bacilli. Oral absorption is good. The protein binding rate of this product is 17% ~ 20%, and the half-life is1~1.3h. In the case of late renal failure, the half-life can be extended to 5 ~ 20h. The usual dosage is 0.5 ~ 1.0g, three times a day, taken orally. [3]
Clinical manifestations of 16. 1 [3]
1. The common adverse reactions are gastrointestinal symptoms such as diarrhea, nausea and vomiting, accounting for about 3. 1%.
2. The incidence of rash is about 2%, and there are still drug fever and asthma. In some cases, serum transaminase is increased, and occasionally eosinophilia and granulocytopenia are seen.
16.2 the key points of treatment for severe hypoxia poisoning are [3]:
1. See related contents of penicillin.
2. Hemodialysis can remove the products in blood, while peritoneal dialysis is ineffective.
17 Pharmacopoeia standard powerful amoxicillin 17. 1 product name 17. 1 Chinese name powerful amoxicillin.
17. 1.2 Chinese pinyin amoxicillin
17. 1.3 English name amoxicillin
17.2 structural formula 17.3 molecular formula and molecular weight c16h19n3o5s 3h2o419.46.
17.4 source (name), content (potency) This product is (2S, 5R, 6r) 3,3 dimethyl 6 [(R) (-) 2 amino 2(4 hydroxyphenyl) acetamido ]7 oxo 4 thio 1 azabicyclo [3.2.0] heptane 2. The content of C 16H 19N3O5S shall not be less than 95.0% in terms of anhydrous substance.
17.5 characteristics this product is white or white-like crystalline powder; It tastes slightly bitter. This product is slightly soluble in water and almost insoluble in ethanol.
Take this product with specific rotation of 17.5. 1, weigh it accurately, add water to dissolve it, dilute it quantitatively, make a solution containing about 2mg per 1ml, and measure it according to law (Appendix VI E of Pharmacopoeia II, 20 10), with specific rotation ranging from +290 to+.
17.6 Identification (1) Take about 0. 125g of this product and amoxicillin reference respectively, add 4.6% sodium bicarbonate solution to dissolve and dilute it, and make a solution containing about 1ml amoxicillin, which is used as the test solution and reference solution; In addition, appropriate amounts of amoxicillin and cefazolin were added to 4.6% sodium bicarbonate solution for dissolution and dilution, and a solution of 10mg amoxicillin and 5mg cefazolin dissolved in 1ml was prepared as the system suitability test solution. According to the test of thin-layer chromatography (appendix ⅴ b of Pharmacopoeia Part II, 20 10), 2μl of each of the above three solutions was absorbed and spotted on the same silica gel GF254 thin-layer plate, with ethyl acetate-acetone-glacial acetic acid-water (5: 2: 2: 1) as the developing agent, developed, dried and placed in 254nm ultraviolet. The system suitability test solution should show two distinct spots, and the position and color of the main spot of the test solution should be the same as that of the control solution.
(2) In the chromatogram recorded under the content determination, the retention time of the main peak of the test solution should be consistent with that of the reference solution.
(3) The infrared absorption spectrum of this product should be consistent with that of the reference substance (Figure 44 1 in the infrared spectrum of the drug).
You can choose one of the above (1) and (2).
17.7 Check the acidity of 17.7. 1 Take this product, add water to make a solution containing 2mg per 1ml, and measure it according to law (Appendix VI H, Part II of Pharmacopoeia 20 10), and the pH value should be 3.5 ~ 5.5.
Clarity of 17.7.2 solution Take 5 copies of this product, each containing 1.0g, add 0.5mol/L hydrochloric acid solution containing 10ml respectively, and observe immediately after dissolution. Take 5 copies of this product, each with 1.0g, and add 10ml of 2mol/L ammonia solution respectively, and observe immediately after dissolution. If there is turbidity, it should not be thicker than turbidity standard solution No.2 (Appendix ⅸ B of Pharmacopoeia Part II, 20 10).
17.7.3 Take an appropriate amount of this product, weigh it accurately, add mobile phase A to dissolve it, and dilute it quantitatively to make a solution containing about 2.0mg per 1ml as the test solution; In addition, an appropriate amount of strong amoxicillin reference substance is taken, accurately weighed, dissolved with mobile phase A, and quantitatively diluted to make a solution containing about 20μg per 1ml as the reference solution. According to high performance liquid chromatography (Pharmacopoeia 20 10, Appendix V D), octadecylsilane bonded silica gel was used as filler. Using 0.05 mol/L phosphate buffer (0.05 mol/L potassium dihydrogen phosphate solution, 2 mol/L potassium hydroxide solution to adjust the pH value to 5.0)- acetonitrile (99: 1) as mobile phase A; Using 0.05mol/L phosphate buffer (pH 5.0) and acetonitrile (80: 20) as mobile phase B; The detection wavelength is 254 nm. First, mobile phase A and mobile phase B (92; 8) Equal volume elution, that is, after the elution of strong amoxicillin peak is completed, elution is performed according to the linear gradient in the table below. Take a proper amount of reference substance for the applicability of the powerful amoxicillin system, add mobile phase A to dissolve and dilute it, make a solution containing about 2.0mg per 1ml, and inject it into the liquid chromatograph for 20μl l.. The recorded chromatogram should be consistent with the standard chromatogram. Inject 20μl of control solution into the liquid chromatograph, and adjust the detection sensitivity to make the peak height of the chromatographic peak of the principal component about 25% of the full scale. Accurately measure 20μl of the test solution and the reference solution, inject them into the liquid chromatograph respectively, and record the chromatogram. If there are impurity peaks in the chromatogram of the test sample, the area of a single impurity peak shall not be greater than the main peak area of the reference solution (1.0%), and the sum of impurity peak areas shall not be greater than 3 times (3.0%) of the main peak area of the reference solution, and any peak in the chromatogram of the test sample shall be less than 0.05 times of the main peak area of the reference solution.
Time (minutes) Mobile phase A(%) Mobile phase B (%) 0 928 20 10/00 40010041928 5592 817.7.4 High-power photo-molecular exclusion chromatography of amoxicillin polymer (Pharmacopoeia II)
Dextran gel G 10 (40 ~ 120μ m) was used as a filler for chromatographic conditions and system suitability test. The inner diameter of the glass column is1.0 ~1.4cm, and the length of the column is 30 ~ 40cm. The mobile phase A is 0.05mol/L phosphate buffer with pH 8.0 (0.05mol/L disodium hydrogen phosphate solution -0.05 mol/L sodium dihydrogen phosphate solution (95: 5)), and the mobile phase B is water, with the flow rate of 65438 0.5 ml/min and the detection wavelength of 254nm. Measure100 ~ 200μ l of 0.2mg/ml blue dextran 2000 solution, inject it into the liquid chromatograph, measure it with mobile phases A and B respectively, and record the chromatogram. According to the blue dextran 2000 peak, the theoretical plate number is not less than 500 and the tailing factor is less than 2.0. The retention time ratio of blue dextran 2000 peak in two mobile phase systems should be between 0.93- 1.07, and the retention time ratio of main peak in control solution and polymer peak in test solution to blue dextran 2000 peak in corresponding chromatographic system should be between 0.93- 1.07. Weigh about 0.2g of amoxicillin, put it in a 10ml volumetric flask, add 4ml of 2% anhydrous sodium carbonate solution to dissolve it, dilute it to scale with 0.3mg/ml blue dextran 2000 solution, and shake well. Measure 100 ~ 200μ l, inject it into a liquid chromatograph, determine it with mobile phase A, and record the chromatogram. The ratio of the peak height of polymer and the valley height of monomer to polymer should be greater than 2.0. In addition, taking mobile phase B as the mobile phase, accurately measure the control solution 100 ~ 200μ L, and inject it continuously for 5 times. The relative standard deviation of peak area should not exceed 5.0%.
17.7.4.2 preparation of control solution take a proper amount of penicillin control substance, weigh it accurately, dissolve it in water, and dilute it quantitatively to make a solution containing about 0.2mg per 1ml.
17.7.4.3 determination method take about 0.2g of this product, accurately weigh it, put it in a 10ml volumetric flask, add 4ml of 2% anhydrous sodium carbonate solution to dissolve it, dilute it to scale with water, shake it evenly, and immediately accurately measure 100 ~ 200μ l and inject it into a chromatograph with mobile phase A as the mobile phase. In addition, accurately measure 100 ~ 200μ l of control solution and inject it into the chromatograph, with mobile phase B as the mobile phase, and determine it by the same method. Calculate the peak area according to the external standard method and divide the result by 10. Amoxicillin-containing polymers shall not exceed 0. 15% (amoxicillin: penicillin 1: 10).
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17.7.5 residual solvents acetone and dichloromethane accurately weigh 0.25g of this product, put it in an empty top bottle, accurately add 5ml of dimethylacetamide to dissolve it, and seal it as the test solution; Accurately weigh an appropriate amount of acetone and dichloromethane, add dimethylacetamide and dilute quantitatively to make a solution containing about 40μg of acetone and 30μg of dichloromethane per 1ml, accurately weigh 5ml, put it in an empty top bottle and seal it as a control solution. According to the residual solvent determination method (the second method in Appendix VIII P of Pharmacopoeia Part II, 20 10). The chromatographic column is a capillary column with 6% cyanopropyl phenyl -94% dimethyl polysiloxane (or similar polarity) as the stationary liquid; The initial temperature is 40℃, which is kept for 4 minutes, and then the temperature is raised to 200℃ at the rate of 30℃ per minute, which is kept for 6 minutes; The inlet temperature is 300℃ and the detector temperature is 250℃. ; The equilibrium temperature of the top empty bottle is 80℃ and the equilibrium time is 30 minutes. Inject the control solution into the headspace and record the chromatogram. The separation degree of acetone and dichloromethane should meet the requirements. Take the test solution and the reference solution for headspace sampling respectively, and record the chromatogram. According to the external standard method, the content of dichloromethane should not exceed 0. 12%, and the content of acetone should meet the requirements.
17.7.6 moisture Take this product, and measure it according to the moisture determination method (Appendix ⅷ M in Pharmacopoeia 20 10, Part II, Method A), and the moisture content should be 12.0% ~ 15.0%.
17.7 Take this product 1.0g residue on ignition and check it according to law (Appendix VIII N of Pharmacopoeia II, 20 10), and the residue shall not exceed 1.0%.
The content of 17.8 was determined by high performance liquid chromatography (appendix ⅴ d, part 2 of Pharmacopoeia 20 10).
17.8. 1 chromatographic conditions and system applicability test uses octadecylsilane bonded silica gel as filler; Using 0.05mol/L potassium dihydrogen phosphate solution (adjusted to pH 5.0 with 2mol/L potassium hydroxide solution)-acetonitrile (97.5∶2.5) as mobile phase; The detection wavelength is 254 nm. Take about 25mg of Adipocillin system suitability reference substance, put it in a 50ml volumetric flask, dissolve it with mobile phase and dilute it to scale, shake it evenly, and inject it into a 20μl liquid chromatograph. The recorded chromatogram should be consistent with the standard chromatogram.
17.8.2 determination method take about 25mg of this product, accurately weigh it, put it in a 50ml volumetric flask, add mobile phase to dissolve and dilute it to scale, shake it evenly, accurately measure 20μl and inject it into a liquid chromatograph, and record the chromatogram; In addition, an appropriate amount of amoxicillin reference substance was taken and determined by the same method. According to the external standard method, calculate the peak area.
17.9 β -lactam antibiotics, penicillins.
17. 10 Store it in the dark and seal it.
17. 1 1 preparation (1) powerful amoxicillin dry suspension? (2) Li Qiang amoxicillin tablets (3) Li Qiang amoxicillin capsules? (4) Li Qiang amoxicillin granules.
Version 17. 12