What Is Norfloxacin?

Norfloxacin (Norfloxacin, also known as Noroxin, Fulgram), aliases: Liloroxol, Haloperic acid, Lexox. Its chemical name is 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -3-quinolinecarboxylic acid. This product is a third-generation quinolone antibacterial drug, which will hinder the function of DNA Gyrase of pathogenic bacteria in the digestive tract, hinder the replication of bacterial DNA, and inhibit bacteria. It is a commonly used medicine for treating enteritis and dysentery. However, this medicine has a retarding effect on the formation of bones in minors and can affect development. It is forbidden for minors to take it.

Drug Name: Norfloxacin
Alias: Lolitol tablets; Lyco small stars

Foreign name: Norfloxacin, AM-715, Brazan, Fulgram, Lexnor, MK-0366, Uroxacin, Noroxin, Zoroxin
Dosage form: Capsule

Norfloxacin compound profile

Norfloxacin Basic Information

Chinese name: Norfloxacin

Chinese alias: Haloperic acid; 1-Ethyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -3-quinolinecarboxylic acid; Ritolol tablets; Lycoxanthin ;; Litolol; Haloperic acid; Lexarcin; Lycocin.

English name: norfloxacin

English alias: 1-ethyl-6-fluoro-7-piperazino-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid; 1-ethyl-6-fluoro-4-oxo-7-piperazinyl-1, 4-dihydro-quinoline-3-carboxylic acid; am-715; Zomxin; Utinor;

CAS number: 70458-96-7

Molecular formula: C ₁₆ H ₁₈ FN ₃ O ₃

Molecular weight: 319.33100

Exact mass: 319.13300

PSA: 74.57000

LogP: 1.66210

Physical and Chemical Properties of Norfloxacin

Appearance and properties: off-white to light yellow crystalline powder

Density: 1.344 g / cm ³

Melting point: 220 ° C

Boiling point: 555.8ºC at 760 mmHg

Flash point: 289.9ºC

Stability: stable under normal temperature and pressure

Storage conditions: ventilated, low temperature and dry

Norfloxacin Safety Information

Customs code: 2933990090

WGK Germany: 2

Danger category code: R20 / 21/22

Safety instructions: S26; S37 / 39

RTECS number: VB2005000

Dangerous goods mark: Xn ^[1]

Norfloxacin production method

O-dichlorobenzene can be obtained by nitration or p-nitrochlorobenzene can be chlorinated to obtain 3,4-dichloronitrobenzene. Then in dimethyl sulfoxide, reflux with potassium fluoride to fluorinate to 3-chloro-4-fluoronitrobenzene. In the presence of hydrochloric acid or acetic acid aqueous solution, iron powder was used to reduce 3-chloro-4-fluoroaniline. Then it is refluxed with triethyl orthoformate and diethyl malonate (to form diethyl ethoxymethylenemalonate) in the presence of ammonium nitrate to obtain a condensation product. Cyclic heating in liquid paraffin or diphenyl ether produces 7-chloro-6-fluoro-4-hydroxyquinoline-3-carboxylic acid ethyl ester. After ethylation, the product is hydrolyzed. Finally, it is condensed with piperazine to obtain norfloxacin. The process is relatively mature and the yield is high, which can generally reach 40% to 65%. However, when a piperazinyl group is introduced at the 7 position, the by-product of the fluorine atom at the 6 position can account for 25%, which is difficult to separate and affects the yield. The total yield based on p-nitrochlorobenzene is over 8%. Before the pyrazine ring was introduced, ethyl 1-ethyl-6-fluoro-7-chloro-1,4-dihydro-4-oxoquinoline-8-carboxylate was first mixed with fluoboric acid or boron trifluoride- The reaction of ether or boron acetate causes the carbonyl group at the 4-position to form a boron chelate, and then the introduction of the pyrazinyl group can reduce the side reactions where the fluorine at the 7-position is replaced, and the yield can be increased by more than 15%, and the quality of the product is improved . The synthesis of norfloxacin has been studied at home and abroad, but not many are actually used in industrial production. The improvement of its synthetic route is mainly reflected in two aspects. The first is to improve the ring formation process, and the second is to make some articles on the introduction of piperazinyl ^[1] .

Norfloxacin uses

Applicable to respiratory tract, urinary tract infection, gonorrhea, prostatitis caused by sensitive bacteria.

Norfloxacin Pharmacopoeia Standard

Norfloxacin source (name), content (potency)

This product is 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7- (1-piperazinyl) -3-quinolinecarboxylic acid. Calculated based on dry products, C16H18FN3O3 should be 98.5% to 102.0%.

Norfloxacin traits

This product is off-white to light yellow crystalline powder; odorless, slightly bitter; hygroscopic.

This product is slightly soluble in dimethylformamide, very slightly soluble in water or ethanol; easily soluble in acetic acid, hydrochloric acid or sodium hydroxide solution.

Melting point

This product has a melting point of 218 to 224 ° C (Annex VIC in Part Two of the 2010 Pharmacopoeia).

Norfloxacin identification

(1) Take an appropriate amount of this product and norfloxacin reference product, add chloroform-methanol (1: 1) respectively to make a solution containing 2.5mg per 1ml, as the test solution and reference solution, thin Layer chromatography (Appendix VB of Part Two of the Pharmacopoeia, 2010 edition) test. Take 10 l of each of the two solutions, point them on the same silica gel G thin plate, and use chloroform-methanol-concentrated ammonia solution (15: 10: 3). As a developing agent, unfold, dry, and inspect under UV light (365nm). The position and fluorescence of the main spot displayed by the test solution should be the same as the position and fluorescence of the main spot of the reference 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.

The above two items (1) and (2) are optional.

Norfloxacin check

Clarity of the solution

Take 5 parts of this product, each 0.5g, and add 10ml sodium hydroxide test solution to dissolve the solution, the solution should be clear; if it is turbid, compare with No. 2 turbidity standard solution (Appendix B of Part Two of the 2010 Pharmacopoeia) concentrated.

relative substance

Take an appropriate amount of this product, accurately weigh it, add an appropriate amount of 0.1mol / L hydrochloric acid solution (1ml of Norfloxacin plus 1ml of 0.1mol / L hydrochloric acid solution) to dissolve, and quantitatively dilute with mobile phase A to make about 0.15 per 1ml A solution of mg was used as the test solution; an appropriate amount was precisely measured and quantitatively diluted with mobile phase A to prepare a solution containing 0.75 g per 1 ml as a control solution. Another 15 mg of impurity A reference is accurately weighed, placed in a 200 ml volumetric flask, dissolved in acetonitrile and diluted to the mark, shake well, take an appropriate amount, and quantitatively dilute with mobile phase A to make a solution containing about 0.3 g per 1 ml. As an impurity A reference solution. As determined by high performance liquid chromatography (Appendix D of Part Two of the Pharmacopoeia 2010), octadecylsilane bonded silica gel was used as a filler; )-Acetonitrile (87:13) is mobile phase A, acetonitrile is mobile phase B; linear gradient elution is performed according to the following table. Weigh appropriate amounts of norfloxacin reference, ciprofloxacin reference and enoxafloxacin reference, add an appropriate amount of 0.1mol / L hydrochloric acid solution to dissolve, and dilute with mobile phase A to make norfloxacin per 1ml A mixed solution of 0.15 mg of ciprofloxacin, 3 g each of ciprofloxacin and enoxacin was taken into a liquid chromatograph, the detection wavelength was 278 nm, and the chromatogram was recorded. The retention time of norfloxacin peak was about 9 minutes. The resolution of the norfloxacin peak and ciprofloxacin peak and the norfloxacin peak and enoxacin peak should be greater than 2.0. Take 20l of the control solution and inject it into the liquid chromatograph, and use 278nm as the detection wavelength to adjust the detection sensitivity so that the peak height of the main component chromatographic peak is about 25% of the full scale. 20 l of each of the test solution, the reference solution and the impurity A reference solution were precisely measured, injected into the liquid chromatograph, and the chromatograms were recorded with the detection wavelengths of 278 nm and 262 nm. If there is an impurity peak in the chromatogram of the test solution, the impurity A (262nm detection) is calculated based on the peak area of the external standard method, which should not exceed 0.2%. The peak area of other single impurities (detected at 278nm) must not be greater than the area of the main peak of the control solution (0.5%); the sum of the peak areas of other impurities (detected at 278nm) must not be greater than twice the area of the main peak of the control solution (1.0%). Any peak that is less than 0.1 times the area of the main peak of the control solution in the chromatogram of the test solution can be ignored.

Time (minutes)	Mobile phase A (%)	Mobile phase B (%)
0	100	0
10	100	0
20	50	50
30	50	50
32	100	0
42	100	0

Loss on drying

Take this product and dry it at 105 to constant weight, and the weight loss shall not exceed 1.0% (Appendix L of Part Two of the Pharmacopoeia of 2010 Edition).

Residue on ignition

Take 1.0g of this product, place it in a platinum crucible, and inspect it according to law (Appendix N of Part Two of the Pharmacopoeia 2010 Edition). The residual residue shall not exceed 0.1%.

Heavy metal

Take the residue left under the item of burning residue and check it according to law (Appendix H of the second edition of the Pharmacopoeia of 2010 Edition, the second method H), containing no more than 15 parts per million of heavy metals.

Determination of Norfloxacin

It was determined by high performance liquid chromatography (Appendix D, Part Two of the Pharmacopoeia, 2010 Edition).

1 Chromatographic conditions and system suitability tests

Octadecylsilane-bonded silica gel was used as a filler; 0.025mol / L phosphoric acid solution (pH adjusted to 3.0 ± 0.1 with triethylamine)-acetonitrile (87:13) was used as the mobile phase, and the detection wavelength was 278nm. Weigh appropriate amounts of norfloxacin reference, ciprofloxacin reference and enoxafloxacin reference, add appropriate amount of 0.1mol / L hydrochloric acid solution to dissolve, dilute with mobile phase to make norfloxacin per 1ml A mixed solution of 25 g, ciprofloxacin, and enoxacin 5 g each was taken into a liquid chromatograph, and the chromatogram was recorded. The retention time of the norfloxacin peak was about 9 minutes. The resolution of the norfloxacin peak and ciprofloxacin peak and the norfloxacin peak and enoxacin peak should be greater than 2.0.

2 Assay

Take about 25mg of this product, accurately weigh it, put it in a 100ml measuring bottle, add 2ml of 0.1mol / L hydrochloric acid solution to dissolve, dilute with water to the mark, shake well, take 5ml precisely, place it in a 50ml measuring bottle, and use mobile phase Dilute to the scale, shake well, accurately measure 20l into the liquid chromatograph, record the chromatogram; take another norfloxacin reference substance, measure the same method, and calculate the peak area according to the external standard method.

Norfloxacin Categories

Quinolones.

Norfloxacin storage

Shaded, sealed and stored in a dry place.

Norfloxacin preparation

(1) Norfloxacin ointment (2) Norfloxacin cream (3) Norfloxacin capsules (4) Norfloxacin eye drops

Norfloxacin

Impurity A: 1-ethyl-6-fluoro-7-chloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ^[2]

Norfloxacin Drug Analysis

Method name:

Determination of Norfloxacin-High Performance Liquid Chromatography

Application:

This method uses high performance liquid chromatography to determine the content of norfloxacin (C ₁₆ H ₁₈ FN ₃ O ₃ ).

This method is applicable to norfloxacin.

Method principle:

The test product was made into a mobile phase solution, and it was subjected to chromatographic separation by a high-performance liquid chromatograph. The absorption value of norfloxacin was measured at a wavelength of 278 nm with an ultraviolet absorption detector, and the content was calculated.

Reagent:

1. 0.025mol / L phosphoric acid solution (adjust the pH to 3.0 ± 0.1 with triethylamine)

Acetonitrile

3. Triethylamine

equipment:

Instrument

1.1 HPLC

1.2 Column

Octadecylsilane-bonded silica gel is used as a filler. The number of theoretical plates calculated based on the ciprofloxacin peak is not less than 2000. The resolution between the norfloxacin peak and the adjacent impurity peaks should meet the requirements.

1.3 UV absorption detector

Chromatographic conditions

2.1 Mobile phase: 0.025mol / L phosphoric acid solution-acetonitrile = 87:13.

2.2 Detection wavelength: 278nm

2.3 Column temperature: room temperature

Sample preparation:

Weigh the test product

25mg of this product was accurately weighed and placed in a 100mL measuring bottle.

2. Preparation of reference solution

Accurately weigh an appropriate amount, add the mobile phase solution to dissolve and make a solution containing 25 g per 1 mL, shake it to obtain.

3. Preparation of test solution

Add 2mL of 0.1mol / L hydrochloric acid solution to the test product to dissolve, add water to dilute to the mark, shake well, take 5mL accurately, place in a 50mL volumetric flask, add mobile phase to dilute to the mark, and shake to obtain.

Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weight taken. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards.

Steps:

20 L of each of the reference solution and the test solution were accurately sucked and injected into a high-performance liquid chromatograph, and the absorption value of ciprofloxacin was measured at a wavelength of 278 nm using an ultraviolet absorption detector. The peak area was calculated according to the external standard method. Got ^[2] .

Norfloxacin drug description

Norfloxacin pharmacology and toxicology

Norfloxacin Lactate

This product is a fluoroquinolone antibacterial drug with broad-spectrum antibacterial effect, especially high antibacterial activity against aerobic gram-negative bacilli, and has good antibacterial effect on the following bacteria in vitro: most bacteria in the family Enterobacteriaceae, including citrate Enterobacteriaceae, Enterobacter cloacae, Enterobacter aerogenes, Escherichia coli, Klebsiella, Proteus, Salmonella, Shigella, Vibrio, Yersinia, etc. Norfloxacin also has antibacterial activity against multi-drug resistant bacteria in vitro. Penicillin-resistant Neisseria gonorrhoeae, Haemophilus influenzae, and Moraxella catarrhalis also have good antibacterial effects. Norfloxacin is a bactericide that acts on the A subunit of bacterial DNA helicase to inhibit DNA synthesis and replication and cause bacterial death.

Norfloxacin pharmacokinetics

Oral absorption is fast but incomplete when fasting, about 30% to 40% of the dose; widely distributed in various tissues and body fluids, such as liver, kidney, lung, prostate, testes, uterus and bile, sputum, blister fluid , Blood, urine, etc., but not seen

Central Nervous System. Serum protein binding rate is 10% to 15%, blood elimination half-life (t1 / 2?) Is 3 to 4 hours, and renal function can be extended to 6 to 9 hours. Single oral administration of 400mg and 800mg of the product, the peak plasma concentration after 1 to 2 hours, the peak plasma concentration (Cmax) was 1.4 ~ 1.6mg / L and 2.5mg / L, respectively. Kidney (glomerular filtration and tubular secretion) and hepatobiliary system are the main excretion pathways. 26% to 32% are excreted from the urine as metabolites and less than 10% as metabolites, and 28% are excreted from bile and / or feces. % To 30%.

Urine pH affects the solubility of the product. Dissolution was minimal at urine pH 7.5, and increased at other pH.

Norfloxacin indications

This norfloxacin is mainly used for the following infections caused by sensitive bacteria:

1. Urogenital infections, including urinary tract infections, prostatitis, acute and chronic pyelonephritis, cystitis, gonorrhea, etc. Among them, suppositories and medicinal films are used for bacterial vaginitis caused by sensitive bacteria; pediatric medicinal powder is used for children's upper and lower urinary tract infections caused by bacteria that are multidrug-resistant and only sensitive to this drug.

2. Digestive system infection, typhoid fever and other gastrointestinal infections caused by Salmonella and cholecystitis.

3. Respiratory infections, such as acute bronchitis, acute exacerbation of chronic bronchitis, and pneumonia.

4. It can also be used for infectious diseases in facial, dermatology, obstetrics and surgery. Eye drops or ointments are used for external eye infections (such as conjunctivitis, keratitis), trachoma, and neonatal acute follicular conjunctivitis caused by sensitive bacteria; injections subconjunctival injection or oral preparations can also be used to treat the eye infection. The ointment is used for impetigo, eczema infection, tinea pedis infection, folliculitis, bloated, etc. It can also control burn granulation wound infection and create conditions for skin grafting.

5. Can also be used as a preventive medicine for abdominal surgery. ^[3]

Norfloxacin contraindications

Patients who are allergic to this product and fluoroquinolones are contraindicated.

Norfloxacin dosage

oral

1. Acute simple lower urinary tract infection caused by Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis 400mg once a day, twice a day, and a course of treatment for 3 days. 2. The dose of simple urinary tract infection caused by other pathogenic bacteria is the same as above, and the course of treatment is 7-10 days.

3 The dose of complex urinary tract infection is the same as above, and the course of treatment is 10 to 21 days.

4 Single gonorrhoea urethritis single 800 ~ 1200mg.

5. Acute and chronic prostatitis is 400 mg once, twice a day for 28 days.

6. Intestinal infections are 300 to 400 mg once, twice a day, and the course of treatment is 5 to 7 days.

7. 800 to 1200 mg of Salmonella typhimurium infection in two to three times a day for 14 to 21 days.

Norfloxacin adverse reactions

1. Gastrointestinal reactions are more common and can manifest as abdominal discomfort or pain, diarrhea, nausea, or vomiting.

2. Central nervous system reactions can include dizziness, headache, drowsiness, or insomnia.

3 Allergic reactions include rash, itching of the skin, and occasionally exudative polyerythema and angioedema. A few patients have photosensitivity.

4 Occasionally:

(1) Seizures, mental disorders, irritability, disturbance of consciousness, hallucinations, tremors.

(2) manifestations of interstitial nephritis such as hematuria, fever, and rash.

(3) Phlebitis.

(4) Crystal urine is more common in high-dose applications.

(5) Joint pain.

5. A few patients can have elevated serum aminotransferases, increased blood urea nitrogen, and decreased peripheral blood elephant white blood cells, mostly mild and transient. ^[4]

Norfloxacin precautions

Summary

1. This product should be taken on an empty stomach and drink 250ml of water at the same time.

DNA 2. Because Escherichia coli is more common in patients resistant to norfloxacin, urine samples should be cultured before administration, and medication should be adjusted with reference to the results of bacterial drug sensitivity.

3 Crystallized urine can occur when the product is used in large doses or when the urine pH is above 7. In order to avoid the occurrence of crystallized urine, it is advisable to drink plenty of water and keep the urine output above 1200ml for 24 hours.

4 Those with impaired renal function need to adjust the dosage according to renal function.

5. Application of fluoroquinolones can cause moderate and severe photosensitivity reactions. Avoid excessive exposure to sunlight when using this product. Discontinue medication if a photosensitivity reaction occurs.

6. Patients with glucose-6-phosphate dehydrogenase deficiency who take this product will most likely develop hemolytic reactions.

glucose Quinolones include this product, which can aggravate the symptoms of myasthenia gravis, respiratory muscle weakness and life-threatening. Patients with myasthenia gravis should be particularly cautious when using quinolones including this product.

8. In the case of liver failure, if it is severe (cirrhotic ascites), the drug clearance can be reduced, the blood drug concentration is increased, and the liver and kidney function are reduced. It is necessary to weigh the advantages and disadvantages and adjust the dose.

9. Patients with previous central nervous system diseases, such as those with epilepsy and history of epilepsy, should avoid the application. When there are indications, the pros and cons should be carefully weighed after application.

Medication for pregnant and lactating women

Monkeys have been used in breeding studies, and the dose was up to 10 times that of humans, and it was found that the product could cause abortion. The peak plasma concentration (Cmax) in monkeys is about twice that of humans. This product has not been confirmed to have teratogenic effects in animals. However, appropriate and well-controlled studies have not been conducted in pregnant women, so this product should not be used in pregnant women.

There is no data on whether the product is secreted by milk. When 200mg of this product was used by a nursing woman, the drug could not be detected in milk. However, because the study dose is small, and other varieties of this class of drugs are secreted by milk, coupled with the potential for serious adverse reactions to newborns and infants, lactating women should avoid using this product or stop breastfeeding during application.

Medication for children

The safety of this product in infants and young children and adolescents under 18 years has not been established. This product is not suitable for children and adolescents under 18 years of age.

Animal medication

However, this product can cause joint disease when used in several young animals.

Medication for elderly patients

Elderly patients often have renal dysfunction, because some of this product is excreted through the kidney, it is necessary to reduce the application.

Norfloxacin drug interactions

1. Urine basifying agents can reduce the solubility of the product in the urine, leading to crystalline urine and renal toxicity.

2. When the product is combined with theophylline, it may be due to the competitive inhibition of the cytochrome P450 binding site, which results in a significant reduction in the liver clearance of theophylline, a prolonged blood elimination half-life (t1 / 2?), An increase in blood concentration, and the appearance of tea. Symptoms of alkalosis, such as nausea, vomiting, tremor, restlessness, agitation, convulsions, palpitations, etc., the theophylline blood concentration and dose adjustment should be measured when combined.

3 The combined use of cyclosporine and this product can increase the blood concentration of the former. The blood concentration of cyclosporine must be monitored and adjusted.

Central nervous system Whole dose.

4 This product can enhance the anticoagulant effect of the anticoagulant warfarin when used together, and the patient's prothrombin time should be closely monitored when combined.

5. Probenecid can reduce the secretion of the product from the renal tubules by about 50%, and when used in combination, it can cause toxicity due to the increased blood concentration of the product.

6. This product has antagonism with furantoin and is not recommended for combined use.

7. Multivitamins, or other preparations containing iron and zinc ions, and antacids containing aluminum or magnesium can reduce the absorption of this product. It is recommended to avoid combined use. If it cannot be avoided, take it 2 hours before the drug or 6 hours after the drug. .

8. Didanosine (DDI) can reduce the oral absorption of this product. Because its preparation contains aluminum and magnesium, it can be chelated with fluoroquinolones, so it is not suitable for use.

9. This product interferes with the metabolism of caffeine, leading to reduced caffeine clearance, prolonged blood elimination half-life (t1 / 2?), And may produce central nervous system toxicity.

Norfloxacin overdose

Mice and rats were administered orally in a single dose of 4 g / kg, and no lethal effect was found. For acute drug overdose, it is necessary to induce vomiting or gastric lavage to promote gastric emptying, carefully observe changes in the condition, and provide symptomatic treatment and supportive therapy. You must maintain a proper rehydration volume.

Norfloxacin case information

Norfloxacin damages the liver

Case Information 1

Male, 50 years old. 5 days ago, due to abdominal discomfort and mushy stool, taking norfloxacin (haloperic acid) 0.2 g orally 3 times a day, nausea occurred after taking the medicine for 2 days (total of 8 pills), general weakness, and paroxysmal abdomen dull pain. On the third day, the skin and sclera were yellow stained, and there were rashes of various sizes. After two days, the rash disappeared, but the jaundice worsened, and urine like strong tea was admitted to the hospital. The patient was healthy and had no history of hepatitis. Examination: body temperature 36.2 , pulse 76 / ^[3]

min, blood pressure 120 / 70mmHg. No abnormalities were found in the heart and lungs, the abdomen was soft, the liver, spleen, and ribs were not touched, and there was no tenderness in the abdomen. Laboratory tests: Alanine aminotransferase 1200U / L, total protein 76.1g / L, albumin 46g / L, globulin 30.1g / L, total bilirubin 180.3mol / L, five negative hepatitis B items. B-ultrasound: no abnormalities in liver, gallbladder, spleen and pancreas. Diagnosis of drug-induced liver damage. That is, intravenous administration of diammonium glycyrrhizinate (Ganlixin) 40mg / d, vitamin C5g / d and other intravenous drip to protect the liver. After 1 week of administration, check for alanine aminotransferase 650U / L, total protein 64.2g / L, albumin 40.1g / L, globulin 24.1g / L, total bilirubin 66.2mol / L, light urine color, continue After 3 weeks of treatment, all the examination indicators returned to normal and the urine color was normal. The patient recovered and was discharged after 1 month. discuss

Norfloxacin is a third-generation quinolone antibacterial. In clinical use, gastrointestinal reactions, peripheral nerve irritation and skin damage are more common. There are few reports about liver function damage caused by norfloxacin. Gu Dezheng's statistical incidence was 5.4%, but the degree of damage in this group of patients was minor, and he improved on his own after stopping the drug. Yin Jian reported a case of severe liver damage with norfloxacin. The patient had a history of allergies to taking norfloxacin. Therefore, the author analyzed that the liver damage after taking norfloxacin was related to the individual's hypersensitivity to the drug. However, in this case, he was in good health and had no history of hepatitis. The skin and sclera yellow stained within 2 days after administration, and severe liver damage occurred. It is suggested that taking a small dose of norfloxacin can cause severe liver damage, and it should be given high attention in the clinic ^[3] .

Case Information 2

Male, 72 years old, was admitted to the hospital for emergency 4h due to abdominal pain and diarrhea. With nausea, vomiting, no fever, palpitations, chest tightness, fatigue, etc., no pain in the liver area. She has a history of chronic atrophic gastritis, chronic bronchitis, and prostatectomy, and her condition is stable. He had no history of hepatitis, tuberculosis, or heart disease. The general condition was acceptable at the time of admission, and the heart and lungs were normal. The liver and spleen are not large, and there is no pain in the liver area. After admission, there were no obvious abnormalities in the abdominal ultrasound and X-rays. The blood routine and liver and kidney function were normal. Acute gastroenteritis was diagnosed. Norfloxacin 0.2 g was given 3 times a day. With other drugs), the symptoms eased, abdominal pain disappeared, and the stool returned to normal. On the 5th day, a review of liver and kidney function revealed GTP538.8mmol / L, GOT516.0mmol / L, and LDH419.7U / L. The patient developed poor gastric appetite, was tired of oil, and had mild fatigue. Repeated examination of liver function showed progressive damage, GPT2080.8mmol / L, GOT1561.5mmol / L, TB122.9mmol / L, DB63.1mol / L, TBA201.6mol / L, ATP186.6U / L, GGT178.8U // L, LDH516.4U / L. Reexamination of the abdominal B ultrasound was normal. Repeated investigations of anti-HAV, HBsAg, anti-HCV, HCV-RNA, hepatitis G, and hepatitis E antibodies were negative, which ruled out the possibility of viral hepatitis. Consider severe liver damage caused by oral norfloxacin. After symptomatic treatment with hepatoprotective therapy, the symptoms gradually eased, liver function returned to normal, and he was discharged from hospital ^[3] .

Expert discussion

Norfloxacin is a third-generation quinolone drug, which has a strong bactericidal effect on gram-negative bacteria. It is commonly used in urinary, intestinal, gynecological, surgical, and facial infections. Side effects are relatively rare, especially serious adverse reactions. . The main adverse reactions of quinolone drugs are:

1. Gastrointestinal reactions.

2. Central response.

3. Kidney damage.

4, large doses or long-term application of this class of drugs are likely to cause liver damage.

The third-generation quinolone drugs are widely used in the clinic because of their broad antibacterial spectrum, less allergic reactions, and mild side effects. In the case of this patient, no other special drugs were applied during the treatment, norfloxacin was discontinued, and liver function improved after hepatoprotective treatment. Viral hepatitis may also be excluded according to clinical manifestations. Its liver function is severely impaired and can be determined to be caused by this drug. In this patient, severe liver damage occurred after oral administration of 0.6g for 6 days, and the GPT reached 2080mmol / L. The severity is rare. There is no such report in China. In this case, the patient is advised that during the application of quinolone drugs, the patient's response should be observed, the liver function should be reviewed in time, and severe liver damage should be found and treated in time. ^[5]

Norfloxacin Helicobacter pylori

Summary

Chronic gastritis and peptic ulcer are closely related to Helicobacterpylori (Hp) infection. Hp-clearing treatment can improve histological inflammation. Although in vitro tests Hp are sensitive to a variety of antibacterial agents, only a few are clinically effective. The third generation of norfloxacin, a third-generation quinolone, has been reported to treat H. pylori-associated gastritis. The purpose of this study was to observe the therapeutic effect of norfloxacin alone and in combination with colloidal bismuth hypocitrate (CBS) on Hp-positive gastritis, and to evaluate the efficacy of serum Hp antibodies (enzyme-linked immunosorbent assay, ELISA method) in determining the efficacy. And application value in follow-up studies ^[3] .

Object

212 patients with Hp-positive chronic gastritis confirmed by gastroscopy histopathology and / or Hp culture. There were 131 males and 81 females. Age 42 years ± 10 years. The main symptoms of 4.3a ± 0.8a were epigastric pain, epigastric distension, belching, nausea or vomiting. Except peptic ulcers, polyps and tumors. History of upper gastrointestinal surgery, irritable bowel syndrome, and other serious systemic diseases were excluded. Antibiotics and colloidal bismuth subcitrate have been taken within 1 month before the test, and women who were breast-feeding or pregnant were also excluded.

method

Histopathological examination: HE staining histological diagnosis of gastroscopy biopsy specimens, and Hp was confirmed by Giemsa staining. Pathological diagnostic criteria refer to the Whitehead method (1979) and the National Collaborative Research Group on Gastric Cancer Prevention and Treatment (1980). The degree of inflammation was judged to be 0, 1, 2, 3 respectively according to normal, mild, moderate, and severe. Bacterial culture: use 10% calf serum Brine broth test tube (3ml per tube) for inspection. Two gastroscopy biopsy tissue blocks were placed. In each case, the biopsy forceps were soaked in disinfectant for 15 minutes and then wiped with alcohol. Hp medium was based on Brinell's agar medium, and defibrinated sheep blood was added with antibiotics. The results were observed 3 days later, and biochemical reactions were identified. Serum Hp antibody detection: ELISA method (modified according to kesumen method). Antigen was sonicated. OD was measured at a wavelength of 492 nm. This group was positive according to the serum dilution 300 (ELISA unit, EU). The specificity of ELISA was identified by absorption test, and no cross-reaction was confirmed with Campylobacter jejuni and Campylobacter colon. Treatment methods Patients with Hp-positive chronic gastritis were randomly divided into 3 groups. The treatment course was 1 month. Group A, 48 males and 24 females, aged 43 ± 10 years old, took norfloxacin 0.2 g, 3 times / d; Group B, 47 males and 23 females, aged 40 years ± 7 years, taking norfloxacin 0.2g and CBS 0.11g, 4 times / d; group C, 46 males and 24 females, age 39 years old ± 9 years old, taking placebo. The condition and adverse drug reactions were recorded weekly. Symptom classification: asymptomatic grade 0, mild grade 1, moderate grade 2 and severe grade 3. Gastroscopy, biopsy pathology, and Hp culture were reviewed 1 month after the treatment was completed, and rechecked 6 months later. Serum Hp antibodies were tested once, 1, 3, and 6 months after withdrawal ^[5] .

Statistical methods used self-control t test (measurement data) and X2 test (counting data).

result

Hp clearance

After one month of treatment, the H. pylori clearance rates of the three groups were: 69% (50/72) in group A; 87% (61/70) in group B; 7% (5/70) in group C. Compared with group C, group A and B2 were significantly higher than group C (P <0.01). The differences between groups A and B2 were also significant (P <0.05). After 6 months of discontinuation, the A and B groups maintained 85% (47/55) and 95% (53/56) Hp negative conversion, respectively. Hp was reproduced in 10% (11/111) of the two groups who had been converted negatively.

Histopathological examination

The changes of inflammation score before and after treatment (1mo, 6mo) in the three groups were: 2.1 ± 0.3, 0.97 ± 0.20, 0.99 ± 0.10 in group A; 2.1 ± 0.5, 0.90 ± 0.21, 0.9 ± 0.4 in group B; 2.02 ± 0.23, 2.0 ± 0.3; 1.9 ± 0.4. The first 2 groups themselves

The differences were significant (P <0.05), and the differences were very significant compared with group C. P <0.01. There was no change in the comparison of group C (P <0.05). Symptom remission rate

At 1mo after treatment, the total symptom relief rate in the three groups was 88% (63/72), 90% (63/70), and 14% (10/70). The A and B2 groups were significantly better than the C group (P <0.01). ). Among them, the most obvious relief of abdominal distension.

Serum Hp antibody titer

After treatment, the drop of Hp antibody in group A and B was significantly decreased (P <0.01), but there was no change in group C (P <0.05), as shown in Table 1. ELISA was compared with Hp culture and / or pathological examination. The sensitivity was 92.4% and the specificity was 89.2%.

Drug sensitivity test

Norfloxacin filter paper susceptibility test (in mm) is 38mm ~ 40mm, while the control polymyxin is 0, neomycin 24mm, furazolidone 44mm ~ 46mm, and tetracycline 28mm ~ 30mm. The minimum inhibitory concentration of norfloxacin (test tube method) was 6.25 g / L to 31.25 g / L. Its 5min killing Hp concentration (plate method) is 250g / ml.

Adverse Drug Reactions There was one case of dizziness in each of the two groups taking norfloxacin, and one case of rash in group A. There were no other adverse reactions in the three groups.

discuss

For Hp-positive chronic gastritis, antibacterial therapy is a new treatment. This study shows that chronic gastritis (especially active gastritis) is closely related to Hp infection. One month after treatment with norfloxacin or combined with CBS, Hp clearance was significantly higher than in the control group. With the elimination of Hp, the histopathological inflammation is reduced and even repaired. It is recommended to use CBS as the base, plus amoxicillin and metronidazole. Although the antibacterial effect is good, the gastrointestinal adverse reactions of the drug are difficult to tolerate, and severe adverse reactions such as fungal stomatitis and Clostridium difficile enteritis often occur. This study was based on the characteristics of good oral absorption of norfloxacin, high blood concentration, strong tissue permeability, less inactivation in the body, and fewer adverse reactions. It is highly sensitive to Hp through in vitro drug sensitivity tests, and has been used clinically for the treatment of chronic gastritis with good results. Of the 111 cases whose Hp was cleared after 1 month of treatment, 90% of them remained negative after 6 months, suggesting that norfloxacin has a good long-term effect.

In this group, the serum Hp antibody was detected by ELISA before and after the use of anti-bacterial therapy, and the antibody titer significantly decreased after antibacterial treatment, which was related to the elimination of Hp and the reduction of inflammation (active inflammation disappeared). It shows that this method has clinical practical value for the determination of drug efficacy, the identification of Hp presence and reproduction. The method is simple, non-invasive, and patient compliance is good. ^[4]