What Is Ampicillin?

Ampicillin, also known as ampicillin and ampicillin, is a beta-lactam antibiotic that can treat a variety of bacterial infections. Indications include respiratory infections, urinary tract infections, meningitis, salmonella infections, and endocarditis. This product can also be used to prevent group B streptococcal infection in newborns. It can be administered orally, intramuscularly and intravenously. Amino penicillin also contains amoxicillin, which penetrates gram-negative bacteria more easily than penicillin or penicillin-resistant penicillin, but is easily broken down by bacterial -lactamase, so it is often used with sulbactam (a -lactam Enzyme inhibitors) to enhance the therapeutic effect on beta-lactamase-producing bacteria. Ampicillin was first discovered in 1961. The drug is listed in the World Health Organization's Essential Drug Standard List and is one of the essential drugs in the basic public health system. In 2014, the wholesale price of each intravenous injection was between approximately $ 0.13 and $ 1.20. This medicine is a scientific medicine, which costs about US $ 13 for a ten-day appointment.

On October 27, 2017, the list of carcinogens published by the International Agency for Research on Cancer of the World Health Organization initially compiled the reference, and ampicillin was included in the list of Class 3 carcinogens. ^[2]

Drug type: Essential medicines
Drug name: Ampicillin

English name: Ampicillin
Chinese alias: Ampicillin; Ampicillin; Ampicillin
English alias: Alpen; Principen; Amperil

Brief introduction of ampicillin compounds

Basic information for Ampicillin

Chinese name Ampicillin

Chinese alias: ampicillin; ampicillin; ampicillin; ampicillin; ampicillin; ambrin; Penicillin trihydrate

English name: ampicillin

English alias: amfipen; qidamp; ay-6108; Ampicillin; binotal

Chemical name: (2S, 5R, 6R) -3,3-dimethyl-6-[(R) -2-amino-2-phenylacetamino] -7-oxo-4-thio-1-azine Heterobicyclo [3.2.o] heptane-2-carboxylic acid trihydrate

Molecular structure formula:

Molecular formula: C ₁₆ H ₁₉ N ₃ O ₄ S·3H ₂ O

Molecular weight: 403

CAS number: 69-53-4

Exact mass: 403.14100

PSA: 165.72000

LogP: 1.15430

Physical and Chemical Properties of Ampicillin

Appearance and properties: odorless white microcrystalline powder with a bitter taste. This product is slightly soluble in water, insoluble in chloroform, ethanol, ether or non-volatile oil; soluble in dilute acid solution or dilute alkali solution.

Density: 1.45

Melting point: 198-200 ° C (dec.) (Lit.)

Boiling point: 683.9ºC at 760 mmHg

Flash point: 367.4ºC

Stability: stable under normal temperature and pressure

Storage conditions: storeroom ventilated, low temperature and dry

Ampicillin Safety Information

Packing grade: I; II; III

Customs Code: 2941109200

WGK Germany: 2

Danger category code: R36 / 37/38; R42 / 43

Safety instructions: S22-S26-S36 / 37

RTECS number: XH8425000

Dangerous goods sign: Xn

Production method of ampicillin

First, the side chain carboxylic acid of D (-)-phenylglycine was treated with PCI5 as a chlorinating agent. Made into acid chloride, and then obtained by condensation reaction with 6-APA. Add acetone and water to the reaction tank, add 6-APA when the temperature drops to -5--10 ° C, and then add phenylglycinyl chloride. After 0.5 h of reaction, adjust the pH to 3.5 with 10% sodium hydroxide. The reaction was extracted with toluene. Take the water layer and adjust the pH to about 3.0 with 10% ammonia. Decolorize with activated carbon and filter. The filtrate was adjusted with ammonia to adjust the pH to 4.8. It was allowed to stand, then filtered, washed with acetone, and dried under vacuum at 40 ° C to obtain a product.

use

For molecular biology and tissue culture ^[1] .

Ampicillin Pharmacopoeia Standard

[Identification] (1) Take an appropriate amount of this product and ampicillin reference substance, add phosphate buffer solution (take 0.50g of anhydrous disodium hydrogen phosphate and 0.301g of potassium digas phosphate, dissolve with water to make 1000ml, pH 7.0 ) Dissolve and dilute to make a solution containing 1 mg in each ml, as the test solution and the reference solution; take the above two solutions and mix them in equal amounts as a mixed solution. According to the thin layer chromatography (Appendix VB) test, take 2µl of each of the three solutions, and point them on the same silica gel G thin layer plate, using acetone-water-toluene-glacial acetic acid (65: 10: 10: 2.5) as the development Agent, unfolded, air-dried, sprayed with 0.3% ninhydrin ethanol color development solution, and heated at 90 ° C until spots appeared. The main spot displayed by the mixed solution shall be a single spot, and the position and color of the main spot displayed by the test solution shall be the same as that of the reference solution or the mixed solution. (2) 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. (3) The infrared light absorption spectrum of this product should be consistent with the control spectrum (spectrum set 6 5 8). The above two items (1) and (2) are optional.

[Check] Take this product for acidity, add water to make a solution containing 2.5 mg per lml, heat on a 60 ° C water bath to dissolve, let cool, and measure according to law (Appendix VI H). The pH value should be 3.5 to 5.5. For the clarity of the solution, take 5 parts of this product, each 0.6 g, and add 5 ml of 1m0l / L hydrochloric acid solution. After dissolving, check immediately, take another 5 parts of this product, each 0.6g, and add 2m0l / L hydroxide solution. 5ml, after dissolution, check immediately, the solution should be clear; if it is turbid, compare with No. 2 turbidity standard solution (Appendix KB), it should not be more concentrated. Take the appropriate amount of this substance, accurately weigh it, add mobile phase A to dissolve and quantitatively dilute it to make a solution containing about 3 mg per lml as the test solution; take another appropriate amount of ampicillin reference substance, accurately weigh, add Mobile phase A was dissolved and quantitatively diluted to prepare a solution containing approximately 30 µg per ml. As determined by high performance liquid chromatography (Appendix VD), octadecylsilane bonded silica gel was used as the filler; mobile phase A was 12% acetic acid solution-0.2 mol / L potassium dihydrogen phosphate solution-acetonitrile-water (0.5: 50: 50: 900); mobile phase B is 12% acetic acid solution-0.2m0l / L potassium dihydrogen phosphate solution-acetonitrile-water (0.5: 50: 400: 550); the detection wavelength is 254nm. Elute first with mobile phase A-mobile phase B (85:15). After the ampicillin peak elutes, perform a linear gradient elution according to the following table. Take an appropriate amount of ampicillin system suitability reference, add mobile phase A to dissolve and dilute it to make a solution containing about 2 mg per ml, and take 20µl into the liquid chromatograph. The recorded chromatogram should be consistent with the standard spectrum. Take the control solution 20µl is injected into the liquid chromatograph, and the detection sensitivity is adjusted so that the peak height of the main component chromatographic peak is about 20% of the full scale. Immediately accurately measure 20 µl of each of the test solution and the control solution, and inject them into the liquid chromatograph respectively to record the chromatogram. If there are impurity peaks in the chromatogram of the test solution, the area of a single impurity peak must not be greater than the area of the main peak of the control solution (1.0%), and the sum of the area of each impurity peak must not be greater than 3 times (3.0%) the area of the main peak of the control solution. Any peak less than 0.05 times the area of the main peak of the control solution in the solution chromatogram is negligible.

N, N-dimethylaniline take about 1.0g of this product, accurately weighed, put in a test tube with a stopper, add 5ml of lm0l / L sodium hydroxide solution, and accurately add the internal standard solution (precision weigh the appropriate amount of naphthalene, add ring Dilute and dilute hexamidine to make a solution containing about 5 µg per 1 ml) 1 ml, shake vigorously, leave it to stand, take the upper liquid as the test solution; take 50 mg of N, N-dimethylaniline, accurately weigh, place In a 50ml volumetric flask, add 2ml of hydrochloric acid and 20ml of water, shake and mix well, then dilute to the mark with water, shake well, take 5ml precisely, place in a 250ml volumetric flask, dilute to the mark with water, shake well, take 1ml accurately In a test tube with a stopper, lml of an internal standard solution was precisely added, shaken vigorously, and allowed to stand, and the upper layer solution was taken as a reference solution. As determined by gas chromatography (Appendix VE), silicone (0V-17) was used as the stationary phase and the coating concentration was 3%; the column temperature was 120 ° C; the N, N-dimethylaniline peak and the internal standard peak were The resolution should meet the requirements. Accurately measure 2µl each of the test solution and the reference solution, and inject them into the gas chromatograph, record the chromatogram, and calculate the peak area ratio according to the internal standard method. N, N-dimethylaniline must not exceed 20 parts per million. Moisture is taken from this product and measured according to the Moisture Determination Method (Appendix M, First Method A). The moisture content should be 12.0% to 15.0%. Take 1.0g of this product and check it according to law (Appendix N). The remaining residue should not exceed 0.5%. The heavy metal shall be taken as the residue left under the burning residue, and shall be inspected in accordance with the law (Appendix H Second Law). The content of heavy metal shall not exceed 20 parts per million.

[Content determination] Determination according to high performance liquid chromatography (Appendix VD). Chromatographic conditions and system suitability tests use octadecylsilicon-bond silica gel as the filler; the mobile phase A-mobile phase B (85:15) under the relevant substance is the mobile phase; the detection wavelength is 254nm. Take appropriate amounts of ampicillin reference and cefradine reference, add mobile phase A to dissolve and make a mixed solution containing about 0.3 mg of ampicillin and cefradine 0.02 mg per 1 ml. Take 20l injection into the liquid chromatography and record the chromatogram. The resolution of the ampicillin peak and the cefradine peak should be greater than 3.0. Take about 50mg of this product by measuring method, accurately weigh it, place it in a 50ml measuring bottle, dissolve with mobile phase A and dilute to the mark, shake well, and accurately measure 20µl into the liquid chromatograph and record the chromatogram; take another ampicillin control Appropriate amount of product, the same method. Calculate the peak area according to the external standard method.

[Category] -lactam antibiotics, penicillins.

[Storage] Sealed and stored in a dry place.

Ampicillin drug description

Pharmacological effects of ampicillin

Ampicillin is a semi-synthetic broad-spectrum penicillin. 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 is better on Streptococcus grass and Enterococcus, but on other bacteria, it is not effective on penicillin-resistant Staphylococcus aureus. Among gram-negative bacteria, Neisseria gonorrhoeae, meningococcus, influenza, Bacillus pertussis, Escherichia coli, typhoid and paratyphoid, dysentery, proteus mirabilis, brucella, etc. are sensitive to this product, but prone to drug resistance Sex. Pneumoniae, indole-positive proteus, and Pseudomonas aeruginosa are not sensitive to this product.

Pharmacokinetics of Ampicillin

After intramuscular injection of 0.5 g, the peak plasma concentration of 12 g / ml was reached in 0.5 to 1 hour; after intravenous injection of 0.5 g, the blood drug concentrations were 17 g / ml and 0.6 g / ml after 15 minutes and 4 hours, respectively. Widely distributed in pleural and peritoneal effusions, joint effusions, aqueous humor and milk, and higher concentrations. The concentration in bile is several times higher than the blood concentration. Can penetrate the placental barrier, but through blood. Cerebrospinal fluid barrier capacity is low. The protein binding rate is 20% to 25%. The half-life is about 1.5 hours, and the half-life of renal insufficiency can be extended to 7-20 hours. 12% to 50% of the drug is metabolized in the liver, partially through the glomerular filtration, and secreted by the renal tubules ^[3] .

It was well absorbed after administration of ampicillin. Normal people take 0.5g, 1g orally on an empty stomach and reach the peak plasma concentration after 2h, which are 5.2g / ml and 7.6g / ml, respectively; intramuscular injection of 0.5g, the peak plasma concentration between 0.5 and 1h, about 12g / ml; After intravenous injection of 0.5g, the blood concentrations of 15min and 4h were 17g / ml and 0.6g / ml, respectively. Neonatal and premature infants received intramuscular injections of 10 mg / kg and 25 mg / kg 1 hour later, and the plasma concentrations reached peak values of 20 g / ml and 60 g / ml, respectively. The drug is widely distributed in the body after absorption. The concentrations of drugs in pleural peritoneal effusion, joint effusion, aqueous humor, and milk were higher. The concentration of ampicillin in the bile is several times higher than the blood concentration; the concentration in the bronchial secretion of patients with pulmonary infection is 1/50 of the blood concentration in the same period; the serum drug concentration in pregnant women is significantly lower than that in pregnancy. Ampicillin can penetrate the placental barrier and maintain a certain blood concentration in amniotic fluid. Ampicillin has a low ability to pass through the normal meninges. Normal cerebrospinal fluid contains only a small amount of drugs, but the drug concentration increases significantly when the meninges are inflamed. The distribution volume of ampicillin was 0.28L / kg, and the protein binding rate was 20% -25%.

The half-life of healthy adults is 1.5h, and the half-life of newborns and preterm infants is 1.0-1.2h. 12% to 50% of the drug is metabolized in the liver. Ampicillin has a slightly slower renal clearance than penicillin, and is partially filtered through the glomerulus and secreted by the renal tubules. In the 24h urine discharge is 20% to 60% in oral, 50% in intramuscular injection and 70% in intravenous injection. In patients with renal insufficiency, the half-life can be extended to 7-20 hours. Hemodialysis can effectively remove the drug, but peritoneal dialysis has no effect on the clearance of ampicillin.

Ampicillin indications

This product is mainly used for urinary system, respiratory system, biliary and intestinal infections caused by sensitive bacteria, as well as meningitis and endocarditis ^[3] .

Contraindications to Ampicillin

Patients who are allergic to ampicillin or other penicillins are contraindicated. Avoid use in patients with infectious mononucleosis, cytomegalovirus infection, lymphocytic leukemia and lymphoma ^[3] .

Ampicillin dosage

Intramuscular injection

For adults, 800,000 to 2 million units per day, divided into 3 to 4 doses.

For children, 25,000 units / kg, administered every 12 hours.

Newborn (term birth): 50,000 units / kg each time, once every 12 hours in the first week of birth, once every 8 hours for more than one week, and once every 6 hours for severe infections.

Intravenous drip

Suitable for severe infections.

Adults, 2 million to 20 million units a day, divided into 2 to 4 intravenous drips. The rate of administration cannot exceed 500,000 units per minute.

Children, 50,000 to 200,000 units / kg per day, divided into 2 to 4 intravenous drips.

Newborn (term delivery): The dosage is the same as that of intramuscular injection.

Adverse reactions to ampicillin

The adverse reactions of ampicillin are similar to penicillin. Allergic reactions are common in rash and urticaria, which is more common than other penicillins. Occasionally, anaphylactic shock, granulocytes, and thrombocytopenia, rare liver function abnormalities, and large doses of intravenous administration can cause neurological symptoms such as convulsions.

Allergic reactions are more common in ampicillin.

1. The rash is the most common adverse reaction, and it usually occurs 5 days after the administration. It shows urticaria or maculopapular rash, the former is a typical rash of penicillin allergic reactions, and the latter has certain specificity for ampicillin. The incidence of injection is higher than that of oral administration.

2. Occasionally caused granulocytes and thrombocytopenia after administration.

3. A few patients can develop interstitial nephritis after medication.

4. A few patients occasionally have abnormal liver function after administration.

5. Large doses of intravenous administration can cause neurological toxicity symptoms such as convulsions. Increased intracranial pressure may occur in infants after administration, manifested as anterior condylar bulge.

6. Ampicillin-related enteritis is extremely rare.

Precautions for Ampicillin

(1) If severe persistent diarrhea occurs during medication, it may be pseudomembranous enteritis, and the drug should be stopped immediately and treated with appropriate antibiotics after diagnosis.

(2) It decomposes quickly in weakly acidic glucose solution, and a neutral infusion solution should be used as a solvent. Use immediately after dissolution.

Other with penicillin:

(1) First ask the history of allergies in detail. People with allergies are generally not suitable for skin tests.

(2) A skin test (concentration of 500 units / ml, intradermal injection of 0.05 to 0.1 ml) should be performed before the medication.

(3) Once anaphylactic shock symptoms occur, 0.1% epinephrine 0.5 ~ 1ml should be injected intramuscularly immediately. If the clinical manifestation does not improve, repeat it half an hour later, and cooperate with other symptomatic treatment.

(4) This product is not suitable for intrathecal injection. It can be administered intramuscularly or intravenously. When an adult's daily dose exceeds 5 million units, it should be painted intravenously. The rate of intravenous administration should not exceed 500,000 units per minute, and it should be instilled in small portions, usually once every 6 hours to avoid central nervous system reactions.

(5) People with a history of allergic diseases such as asthma, eczema, hay fever, urticaria, etc. should be used with caution. Those with severe renal impairment should adjust the dose or extend the interval between administrations.

(6) When administering large doses, it should be taken into account that the sodium or potassium ions brought in can cause hypernatremia or hyperkalemia. One million units of penicillin sodium contains 1.7 mmol (39 mg) of sodium ions; one million units of penicillin G potassium contains 1.5 mmol (65 mg) of potassium ions.

(7) The aqueous solution of this product is unstable and easily hydrolyzed, so the injection solution should be prepared fresh. When it must be stored, it should be refrigerated and used up within 24 hours.

Ampicillin drug interactions

(1) Combined with probenecid, aspirin, indomethacin and sulfa drugs, can reduce the excretion of penicillin drugs, increase the concentration of penicillin blood, enhance the effect, but may also increase the toxicity.

(2) Combined with bacteriostatic drugs such as tetracycline, erythromycin, chloramphenicol and sulfonamides, it may reduce the antibacterial effect of this product.

The combined effect of ampicillin and chloramphenicol on the antibacterial effect of influenzae in vitro varies. Chloramphenicol has no antagonistic effect on ampicillin at high concentrations (5 to 10 mg / L), and it can weaken the bactericidal effect of ampicillin at low concentrations (1 to 2 mg / L), but has no antibacterial effect on chloramphenicol. influences. And when the two drugs are combined for the treatment of bacterial meningitis, the incidence of long-term sequelae is higher than when the two drugs are used alone.

(3) Combined with warfarin, it can strengthen the anticoagulant effect.

(4) Taking contraceptives at the same time may affect the contraceptive effect.

Ampicillin can stimulate estrogen metabolism or reduce its enterohepatic circulation and reduce the effectiveness of oral contraceptives.

(5) Kanamycin can enhance the in vitro antibacterial effect of ampicillin on Escherichia coli, Proteus and Enterobacter.

(6) Gentamicin can enhance the in vitro bactericidal effect of ampicillin on group B streptococci.

(7) The combination of ampicillin and clavulanic acid can reduce the minimum inhibitory concentration of -lactamase-producing gonococci from 64 g / ml to 4 g / ml.

(8) Lincomycin can inhibit the antibacterial effect of ampicillin on Staphylococcus aureus in vitro.

(9) Allopurinol can increase the incidence of ampicillin skin and mucosal reactions, especially in hyperuricemia patients.

(10) Chloroquine can reduce the absorption of ampicillin by 19% to 29%.

(11) Ampicillin decomposes quickly in weakly acidic glucose solution, and a neutral liquid should be used as a solvent.

Ampicillin poisoning

Ampicillin (ampicillin, ampicillin) is used to treat respiratory, gastrointestinal, urinary, soft tissue, meningitis, sepsis and endocarditis infections caused by sensitive bacteria. Can be used orally, intramuscularly or intravenously. It is well distributed after absorption, and effective concentrations can be reached in cerebrospinal fluid, pleural and ascites fluid, joint cavity, and bronchial secretion after injection. The plasma protein binding rate is 20%, and the half-life is 1-5 hours. The usual dose for adults is 2 to 4 g / d, divided into 4 oral administrations; intramuscular injection of 4 to 6 g / d, divided into 4 equal times; intravenous drip 4 to 12 g, divided into 2 to 4 times.

Clinical manifestation

1. Adverse reactions are more common in allergic reactions. Among them, the rash is the most common, with an incidence rate of 3.1% to 18%, which usually appears 7 to 12 days after the start of treatment, showing urticaria or maculopapular rash. The incidence of rash was higher by injection than by oral administration. Renal insufficiency also has a high incidence of rashes. There have been reports of exfoliative dermatitis. It has been reported that allergic dermatitis occurred in 8 cases with liver damage of varying degrees. Allergic liver damage should be considered.

2. It has been reported that a patient's original hypertension worsened during the intravenous injection, rising from 130/90 mmHg to 230/130 mmHg, with chest tightness and severe head pain.

3. Urinary tract infections may cause double infection of Proteus, Aerobacter and Candida albicans.

treatment

The main points of treatment for ampicillin poisoning are:

1. The principle of treatment of adverse reactions is the same as penicillin.

2. Hemodialysis can effectively remove the product from the blood, and peritoneal dialysis is not effective ^[4] .

Ampicillin preparation

(1) (potassium salt) sterile powder for injection: 0.25g (400,000 units); 0.5g (800,000 units).

(2) (Sodium salt) sterile powder for injection: 0.24g (400,000 units); 0.48g (800,000 units); 0.96g (1.6 million units).

^[5-8]