2 English reference ampicillin
3 Overview Ampicillin is a semi-synthetic broad-spectrum penicillin, which belongs to β -lactam antibiotics and ampicillin. Ampicillin is white crystalline powder; It tastes slightly bitter. Its antibacterial mechanism is the same as penicillin, characterized by broad spectrum and intolerance to penicillinase. Can be used for treating infections such as respiratory tract, gastrointestinal tract, urinary tract, soft tissue, meningitis, septicemia and endocarditis caused by sensitive bacteria. It can be administered orally, intramuscularly or intravenously. It is evenly distributed after absorption, and can reach effective therapeutic concentration in cerebrospinal fluid, pleural effusion, joint cavity and bronchial secretions after injection.
Ampicillin is a national essential drug.
4 common name of ampicillin
5 English name ampicillin
6 ampicillin, alias ampicillin; Ambien; Ampicillin; An Bixian; Ambien; An Bixian; An Bixin; Ampicillin; Ampicillin; Ampicillin trihydrate; Ampicillin trihydrate; Ampicillin trihydrate; Ampicillin trihydrate; Benasho
Classification of Antibacterials >: β -lactam antibiotics >:? Penicillins? & gt？ Semi-synthetic penicillins
8 pharmacological effects of ampicillin ampicillin is a semi-synthetic broad-spectrum penicillin, and its antibacterial mechanism is to prevent the cell wall synthesis of bacteria, so it can not only inhibit its proliferation, but also directly kill bacteria. The effect on Gram-positive bacteria is similar to that of penicillin, and it has a better effect on Streptococcus viridans and Enterococcus, but it has a worse effect on other bacteria, but it is ineffective on penicillin-resistant Staphylococcus aureus. Gram-negative bacteria such as Neisseria gonorrhoeae, Meningococcus, Influenza Bacillus, Pertussis Bacillus, Escherichia coli, Typhoid and Paratyphoid Bacillus, Dysentery Bacillus, Proteus mirabilis, Brucella, etc. Sensitive to this product, but prone to drug resistance. Pneumonia, indole-positive Proteus and Pseudomonas aeruginosa are not sensitive to this product. [ 1]
9 Pharmacokinetics After intramuscular injection of 0.5g, the peak plasma concentration reached12μ g/ml within 0.5 ~ 1 hour; After intravenous injection of 0.5g, the plasma concentrations of 15min and 4h were 17μg/ml and 0.6μg/ml, respectively. Widely distributed in pleural effusion, joint effusion, aqueous humor and milk, with high concentration. The concentration in bile is several times higher than that in blood. It can penetrate the placental barrier, but its ability to penetrate the blood and cerebrospinal fluid barrier is low. Protein binding rate is 20% ~ 25%. The half-life is about 1.5 hours, and the half-life of renal insufficiency can be extended to 7 ~ 20 hours. 12% ~ 50% drugs are metabolized in the liver, and some drugs are secreted by glomerular filtration and renal tubules. [ 1]
Ampicillin was well absorbed after administration. Normal people took 0.5g and 1g orally on an empty stomach, and reached the peak of blood concentration 2 hours later, which were 5.2μg/ml and 7.6μ g/ml respectively. Intramuscular injection of 0.5g lasted for 0.5 ~ 1h and reached the peak of blood concentration, which was about 12μ g/ml. After intravenous injection of 0.5g, the plasma concentrations of 15min and 4h were 17μg/ml and 0.6μg/ml, respectively. After 10mg/kg and 25mg/kg intramuscular injection 1h, the plasma concentration reached the peak, which were 20μg/ml and 60μg/ml respectively. Drugs are widely distributed in the body after absorption. The concentration of drugs in pleural effusion, joint cavity effusion, aqueous humor and milk is high. The concentration of ampicillin in bile is several times higher than that in blood. The concentration of bronchial secretions in patients with pulmonary infection is1/50 of the blood drug concentration in the same period; The drug concentration in pregnant women's serum was significantly lower than that during pregnancy. Ampicillin can penetrate the placental barrier and maintain a certain blood concentration in amniotic fluid. The ability of ampicillin to penetrate normal meninges is low, and normal cerebrospinal fluid contains only a small amount of drugs, but the drug concentration increases obviously when meninges are inflamed. The distribution volume of ampicillin is 0.28L/kg, and the protein binding rate is 20% ~ 25%.
The half-life of healthy adults is 1.5h, and that of newborns and premature infants is1.0 ~1.2h ...12% ~ 50% of drugs are metabolized in the liver. The renal clearance rate of ampicillin is slightly slower than that of penicillin, and part of it is secreted by glomerular filtration and renal tubules. The 24-hour urinary excretion rate is 20% ~ 60% by oral administration, 50% by intramuscular injection and 70% by intravenous injection. In patients with renal insufficiency, the half-life can be extended to 7 to 20 hours. Hemodialysis can effectively remove drugs, while peritoneal dialysis has no effect on the removal of ampicillin.
Indications 10 ampicillin is mainly used for urinary system, respiratory system and intestinal infection caused by sensitive bacteria, as well as meningitis, soft tissue infection, sepsis and endocarditis. [ 1]
1 1 contraindications are prohibited for patients who are allergic to ampicillin or other penicillins, and are contraindicated for patients with infectious mononucleosis, cytomegalovirus infection, lymphocytic leukemia and lymphoma. [ 1]
12 Precautions (1) If severe persistent diarrhea occurs during medication, which may be pseudomembranous enteritis, you should stop taking the medicine immediately and use the corresponding antibiotics after diagnosis [1].
(2) It decomposes quickly in weakly acidic glucose solution, so neutral infusion should be chosen as the solvent. Use immediately after dissolution. [ 1]
Others use penicillin [2]:
(1) First, ask the allergic history in detail. People with a history of allergies are generally not suitable for skin tests.
(2) The skin test should be carried out according to the specified method (concentration is 500 units/ml, intradermal injection is 0.05 ~ 0. 1 ml).
(3) In case of anaphylactic shock, 0. 1% adrenaline 0.5 ~ 1 ml should be injected immediately. If the clinical manifestations are not improved, it should be repeated 1 time after half an hour, and other symptomatic treatments should be combined.
(4) This product is not suitable for intrathecal injection, but can be injected intramuscularly or intravenously. When the daily dose of adults exceeds 5 million units, it should be applied by intravenous injection. The speed of intravenous administration should not exceed 500,000 units per minute, and it should be rapidly dripped several times, generally every 6 hours 1 time, to avoid central nervous system reaction.
(5) Patients with a history of allergic diseases such as asthma, eczema, hay fever and urticaria should use it with caution, and those with severe renal function damage should adjust the dosage or extend the administration interval.
(6) When taking large doses of drugs, it should be considered that sodium ions or potassium ions brought in can cause hypernatremia or hyperkalemia. Penicillin sodium 1 10,000 units containing sodium ion 1.7 mmol (39 mg); Penicillin G potassium 1 10,000 units contains potassium ion 1.5mmol (65mg).
(7) The aqueous solution of this product is unstable and easy to hydrolyze, and the injection should be freshly prepared. If it must be preserved, it should be refrigerated in the refrigerator and used up within 24 hours.
Adverse reactions of 13 The adverse reactions of ampicillin are similar to those of penicillin, and allergic reactions are common in rash and urticaria, which is higher than other penicillins. Occasionally anaphylactic shock, granulocytopenia and thrombocytopenia, abnormal liver function are rare, and nervous system symptoms such as convulsions may occur after high-dose intravenous administration. [ 1]
Allergic reaction is the most common adverse reaction of ampicillin.
1. Rash is the most common adverse reaction, which mostly occurs on the fifth day after medication, showing urticaria or maculopapular rash. The former is a typical allergic reaction rash of penicillin, while the latter is specific to ampicillin. The incidence of injection administration is higher than that of oral administration.
2. Occasional granulocytopenia and thrombocytopenia after medication.
3. Interstitial nephritis can appear in a few patients after taking the medicine.
4. A few patients occasionally have abnormal liver function after taking medicine.
5. High-dose intravenous administration can cause nervous system poisoning symptoms such as convulsion. After taking the medicine, infants may have increased intracranial pressure, which is manifested as anterior fontanel protuberance.
6. Ampicillin-associated enteritis is extremely rare.
14 dosage form specifications (1) (potassium salt) sterile powder for injection: ① 0.25g (40 400,000 units); ② 0.5g (80 800,000 units).
(2) (sodium salt) sterile powder for injection: ① 0.24g (40 400,000 units); ② 0.48g (80 800,000 sets); ③ 0.96g (6.5438+0.6 million units).
Administration and dosage 15 ampicillin 15. 1 intramuscular injection [1]
① Adults, 800,000 ~ 2 million units per day, administered 3 ~ 4 times.
② Children, 25,000 units /kg, once every 1.2 hours.
③ Newborn (full-term delivery): 50,000 units /kg each time, every 12 hours/kloc-0 times in the first week of birth, every 8 hours/kloc-0 times for more than one week, and every 6 hours/kloc-0 times for severe infection.
15.2 intravenous drip [1]
It is suitable for severe infection.
① Adults, 2 million ~ 20 million units per day, divided into 2 ~ 4 intravenous drip. The administration rate should not exceed 500,000 units per minute.
② Children, 500,000 ~ 200,000 units /kg daily, intravenous drip 2 ~ 4 times.
③ Newborns (full-term delivery): The dosage is the same as intramuscular injection.
16 drug interaction (1) combined with probenecid, aspirin, indomethacin and sulfonamides can reduce the excretion of penicillins, increase their blood concentration and enhance their effects, but the toxic reaction may also increase [1].
(2) Combination with tetracycline, erythromycin, chloramphenicol and sulfonamides may reduce the antibacterial effect of this product [1].
After ampicillin combined with chloramphenicol, the antibacterial effect on influenza Bacillus in vitro is different. Chloramphenicol has no antagonistic effect on ampicillin at high concentration (5 ~ 10 mg/L), but it can weaken the bactericidal effect of ampicillin at low concentration (1 ~ 2 mg/L), but it has no effect on the antibacterial effect of chloramphenicol. And when the two drugs are used together to treat bacterial meningitis, the incidence of long-term sequelae is higher than that when the two drugs are used alone.
(3) Combined with warfarin, anticoagulation can be enhanced [1].
(4) Taking contraceptives at the same time may affect the contraceptive effect [1].
Ampicillin can metabolize estrogen or reduce its intestinal and hepatic circulation, thus reducing the efficacy of oral contraceptives.
(5) Kanamycin can enhance the antibacterial effect of ampicillin on Escherichia coli, Proteus and Enterobacter in vitro.
(6) Gentamicin can enhance the bactericidal effect of ampicillin on group B streptococcus in vitro.
(7) The combination of ampicillin and clavulanic acid can reduce the minimum inhibitory concentration of β -lactamase-producing Neisseria gonorrhoeae from 64μg/ml to 4μg/ml.
(8) Lincomycin can inhibit the antibacterial effect of ampicillin on Staphylococcus aureus in vitro.
(9) Allopurinol can increase the incidence of skin mucosal reaction of ampicillin, especially in patients with hyperuricemia.
(10) chloroquine can reduce the absorption of ampicillin 19% ~ 29%.
(1 1) ampicillin decomposes rapidly in weakly acidic glucose solution, so neutral solution should be used as solvent.
17 ampicillin is stored and dried, and kept away from light. Don't put it in the refrigerator to prevent bottled products from absorbing moisture. [ 1]
The clinical application of 18 ampicillin is suitable for the treatment of general mild infection. Commonly used for acute urinary tract infections caused by Neisseria gonorrhoeae, Escherichia coli, Proteus and Enterococcus. Combined with aminoglycoside antibiotics is effective in the treatment of enterococcal endocarditis.
19 ampicillin poisoning ampicillin (ampicillin, ampicillin) is used to treat infections such as respiratory tract, gastrointestinal tract, urinary tract, soft tissue, meningitis, sepsis and endocarditis caused by sensitive bacteria. It can be administered orally, intramuscularly or intravenously. It is evenly distributed after absorption, and can reach effective therapeutic concentration in cerebrospinal fluid, pleural effusion, joint cavity and bronchial secretions after injection. The binding rate of plasma protein is 20%, and the half-life is L ~1.5h. The usual dose for adults is 2 ~ 4g/d, taken orally for 4 times. Intramuscular injection of 4 ~ 6g/d, divided into 4 times; Intravenous drip 4 ~ 12g, divided into 2 ~ 4 times. [3]
Clinical manifestations of 19. 1 [4]
1. Allergic reaction is the most common adverse reaction. Among them, rash is the most common, the incidence rate is 3. 1% ~ 18%, which often appears 7 ~ 12 days after the start of treatment, showing urticaria or maculopapular rash. The incidence of rash by injection is higher than that by oral administration. Patients with renal insufficiency also have a high incidence of rash. Exfoliative dermatitis has been reported. It has been reported that 8 cases of allergic dermatitis have different degrees of liver function damage, which should be considered as allergic liver injury.
2. It is reported that a patient's primary hypertension deteriorated from 130/90 mmHg to 230/ 130/90 mmHg during intravenous injection, accompanied by chest tightness and severe headache.
3. Patients with urinary tract infection can have double infections of Proteus, Aeromonas and Candida albicans.
19.2 the treatment points of ampicillin poisoning are [5]:
1. The principle of handling adverse reactions is the same as that of penicillin.
2. Hemodialysis can effectively remove this product from blood, while peritoneal dialysis is ineffective.
20 pharmacopoeia standard ampicillin 20. 1 product name 20. 1. 1 Chinese name ampicillin
20. 1.2 Chinese Pinyin Anbian Xilin
20. 1.3 English name ampicillin
20.2 structural formula 20.3 molecular formula and molecular weight c16h19N3O4S3H2O 403.45
20.4 Source (name) and content (potency) This product is (2S, 5R, 6r) 3,3 dimethyl 6[(R)2 amino 2 phenylacetylamino ]7 oxo 4 thio 1 azabicyclo [3.2.0] heptane 2 formic acid trihydrate. The content of ampicillin (C 16H 19N3O4S) shall not be less than 96.0% in terms of anhydrous substance.
20.5 Characteristics This product is white crystalline powder; It tastes slightly bitter.
This product is slightly soluble in water and insoluble in chloroform, ethanol, ether or volatile oil; Soluble in dilute acid solution or dilute alkali solution.
20.5. 1 specific rotation Take this product, accurately weigh it, add water to dissolve it, dilute it quantitatively, make a solution containing about 2.5mg per 1ml, heat it in a water bath at 60℃ to dissolve it, cool it, and determine it according to law (Appendix ⅵ E of Pharmacopoeia Part II, 20 10 edition), and the specific rotation is +280.
20.6 Identification (1) Take an appropriate amount of this product and ampicillin reference substance, add phosphate buffer (take 0.50g anhydrous disodium hydrogen phosphate and 0.30 1g potassium dihydrogen phosphate, and dissolve them in water to make 1000ml, with a pH value of 7.0), dissolve and dilute to1. Take the above two solutions, and mix them in equal amount to form a mixed 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, respectively, on the same silica gel G thin-layer plate, and acetone-water-toluene-glacial acetic acid (65:10:/kloc-0: 2.5) was used as the developing agent. The main spot in the mixed solution should be a single spot, and the position and color of the main spot in the test solution should be the same as that in the control solution or mixed 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 658: Collection of infrared spectrum of drugs).
You can choose one of the above (1) and (2).
20.7 Check the acidity of 20.7. 1 Take this product, add water to make a solution containing 2.5mg per 1ml, heat it in a water bath at 60℃ to dissolve it, let it cool, and determine it according to law (Appendix 6 h of Pharmacopoeia Part II, 20 10), and the pH value should be 3.5 ~ 5.5.
20.7.2 Solution clarity Take 5 copies of this product, each with 0.6g, add 5ml 1mol/L hydrochloric acid solution respectively, and check immediately after dissolution. Take 5 copies of this product, 0.6g each, and add 5m2mol/L ammonium hydroxide solution respectively, and check immediately after dissolution. All solutions shall be clarified; If there is turbidity, it should not be thicker than turbidity standard solution No.2 (Appendix ⅸ B of Pharmacopoeia Part II, 20 10).
20.7.3 Take an appropriate amount of related substances of this product, weigh it accurately, add mobile phase A to dissolve it, and dilute it quantitatively to make a solution containing about 3mg per 1ml as the test solution; Take an appropriate amount of ampicillin reference substance, accurately weigh it, add mobile phase A to dissolve it, and dilute it quantitatively to make a solution containing about 30μg 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. The mobile phase a is/kloc-0.2% acetic acid solution -0.2 mol/L potassium dihydrogen phosphate solution-acetonitrile-water (0.5; 50:50; 900); The mobile phase b is/kloc-0.2% acetic acid solution -0.2 mol/L potassium dihydrogen phosphate solution-acetonitrile-water (0.5: 50: 400: 550); The detection wavelength is 254 nm. Elute with mobile phase A and mobile phase B (85: 15) in equal amount, and perform linear gradient elution according to the following table immediately after LAM Raymond elution. Take an appropriate amount of reference substance suitable for ampicillin system, add mobile phase A to dissolve and dilute it to make a solution containing about 2mg per kloc-0/ml, and inject 20μl into the liquid chromatograph. 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 principal component chromatography about 20% of the full scale. Immediately and 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 the impurity peak areas shall not be greater than 3 times (3.0%) of the main peak area of the reference solution. Any peak less than 0.05 times of 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 8515 30100 450100 50 8515 60 8515 20.7.4n, n Add 5ml 1mol/L sodium hydroxide solution, accurately add internal standard solution (accurately weigh appropriate amount of naphthalene, add cyclohexane to dissolve and dilute to make a solution containing about 50μg per 1ml), shake vigorously, stand still, and take the upper liquid as the test solution; Take 50mg of N, N dimethylaniline, accurately weigh it, put it in a 50ml volumetric flask, add 2ml of hydrochloric acid and 20ml of water, shake it evenly, dilute it to scale with water, accurately measure 5ml, put it in a 250ml volumetric flask, dilute it to scale with water, shake it evenly, accurately measure 65438 0ml, put it in a test tube with a plug, and add 5ml 1 mol/L. The resolution of N, N dimethylaniline peak and internal standard peak should meet the requirements. Accurately measure 2μl of test solution and reference solution, inject them into the gas chromatograph respectively, record the chromatogram, and calculate the peak area ratio according to the internal standard method. The content of N, N dimethylaniline shall not exceed 20 parts per million.
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20.7.5 Moisture Take this product and measure it according to the moisture determination method (Appendix Ⅷ m, Method A, Part II of Pharmacopoeia 20 10). The water content should be 12.0% ~ 15.0%.
20.7.6 Take this product 1.0g as residue on ignition, and check it according to law (Appendix VIII N of Pharmacopoeia II, 20 10), and the residue shall not exceed 0.5%.
20.7.7 Take the residue left under the heavy metal residue on ignition and check it according to law (the second method in Appendix VIII H of Pharmacopoeia 20 10), and the content of heavy metals shall not exceed 20 parts per million.
20.8 the content was determined by high performance liquid chromatography (appendix ⅴ D, part ii, pharmacopoeia 20 10).
20.8. 1 chromatographic conditions and system applicability test uses octadecylsilane bonded silica gel as filler; Mobile phase A and mobile phase B (85: 15) under related substances are used as mobile phases; The detection wavelength is 254 nm. Take a proper amount of ampicillin and cefradine reference substance, add mobile phase A to dissolve them, and make a mixed solution containing about 0.3mg of ampicillin and 0.02mg of cefradine per kloc-0/ml. Take 20μl and inject it into a liquid chromatograph, and record the chromatogram. The resolution of ampicillin peak and cefradine peak should be greater than 3.0.
20.8.2 Determination method Take about 50mg of this product, accurately weigh it, put it in a 50ml volumetric flask, dissolve it with mobile phase A and dilute it to scale, shake it evenly, accurately measure 20ml and inject it into a liquid chromatograph, and record the chromatogram; In addition, an appropriate amount of ampicillin reference substance was taken and determined by the same method. Calculate the peak area according to the external standard method.
Class 20.9 β -lactam antibiotics and penicillins.
20. Store 20. 10/0 away from light and sealed in a dry place.
20. 1 1 version