What Is Metronidazole?

Metronidazole is mainly used to treat or prevent systemic or local infections caused by the above anaerobic bacteria, such as anaerobic infections in the abdominal cavity, digestive tract, female reproductive system, lower respiratory tract, skin and soft tissues, bones and joints. Sepsis, endocarditis, meningeal infections, and colitis caused by antibiotics are also effective. Tetanus is often used in combination with tetanus antitoxin (TAT). Can also be used for oral anaerobic infections.

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 metronidazole was in the list of 2B carcinogens. ^[1]

Chinese name: metronidazole

Chinese alias: 1- (2-hydroxyethyl) -2-methyl-5-nitroimidazole; 2-methyl-5-nitro-1H-imidazole-1-ethanol; 2- (2-methyl- 4-nitro-1-imidazolyl) ethanol; metronidazole; metronidazole; furnazide; metronidazole; midazolone; metronidazole; nitrohydroxyacetazole; Metronidazole; Frege;

English name: metronidazole

English alias: 2-methyl-5-nitroimidazole-1-ethanol; Eumin; Bexon; Klont; 1H-Imidazole-1-ethanol, 2-methyl-5-nitro-; Metronazole; Atrivyl; Clont; FLACYL; Klion; Meronidal; Thivazol

CAS number: 443-48-1

Molecular formula: C ₆ H ₉ N ₃ O ₃

Molecular weight: 171.15400

Structural formula:

[Identification] (1) Take about 10mg of this product, add 2ml of sodium hydroxide test solution at a mild temperature to obtain a purple-red solution; add dilute hydrochloric acid to make it acidic and turn yellow, and then add excess sodium hydroxide test solution to change Into orange-red. (2) Take about 0.1g of this product, add 4ml of sulfuric acid solution (3 100), it should be able to dissolve; add 10ml of trinitrophenol test solution, and a yellow precipitate will be formed after standing. (3) Take the solution under the absorption coefficient and measure it according to the ultraviolet-visible spectrophotometry (Appendix IVA). It has the maximum absorption at the wavelength of 277nm and the minimum absorption at the wavelength of 241nm. (4) The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 112).

[Check] Clarity and color of ethanol solution Take this product, add ethanol to dissolve and dilute it to a solution containing about 5mg per 1ml, the solution should be clear; if it is turbid, compare with turbidity standard solution No. 1 (Appendix B) It must not be thicker; if it is colored, it must not be deeper than the yellow or yellow-green standard colorimetric solution (Appendix A). Related substances are protected from light. Take about 100mg of this product, put it in a 100ml measuring bottle, add methanol to dissolve and dilute to the mark, shake well, take an appropriate amount, and dilute with mobile phase to make a solution containing 0.2mg per 1ml, as the test solution; Take about 20mg of 2-methyl-5-nitroimidazole reference substance, put it in a 100ml volumetric flask, add methanol to dissolve and dilute to the mark, shake well, and use it as a reference substance solution. Take 2ml of the test solution and 1ml of the reference solution accurately, place them in the same 100ml volumetric flask, dilute to the mark with mobile phase, shake well, take 5ml precisely, place them in a 50ml volumetric flask, and dilute to the mark with mobile phase Shake well as control solution. Measured according to high performance liquid chromatography (Appendix VD), using octadecylsilane bonded silica as a filler, methanol-water (20:80) as the mobile phase, and the detection wavelength is 315nm. The calculation of the azole peak is not less than 2000, and the resolution of the metronidazole peak and the 2-methyl-5-nitroimidazole peak should not be less than 2.0. Take 20l of the control solution and inject it into the liquid chromatograph, adjust the detection sensitivity so that the peak height of the metronidazole chromatographic peak is 10% of the full range; then accurately measure 20l each of the test solution and the control solution, and inject them into the liquid chromatograph Record the retention time of the chromatogram to the main component peak twice. If there is a chromatographic peak with the same retention time as 2-methyl-5-nitroimidazole in the chromatogram of the test solution, the peak area must not be greater than 0.5 times (0.1%) of the metronidazole peak area in the control solution; The sum of the peak areas of impurities must not be greater than the metronidazole peak area (0.2%) in the control solution. Loss on drying: Take this product and dry to constant weight at 105 . Lose weight should not exceed 0.5% (Appendix L). Take 1.0g of this product and check it according to law (Appendix N). The remaining residue should not exceed 0.1%. 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 method). The content of heavy metal shall not exceed 10 parts per million.

[Content determination] Take about 0.13g of this product, accurately weigh, add 10ml of glacial acetic acid to dissolve, add 2 drops of naphthol benzyl alcohol indicator solution, titrate with perchloric acid titration solution (0.1mol / L) until the solution becomes green, The results of the titration are corrected with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 17.12mg of C6H9N3O3.

[Category] Anti-anaerobic drugs, anti-trichomonal drugs.

Metronidazole pharmacology

In addition to its resistance to trichomoniasis and amoebia, in recent years, it has been widely used to resist anaerobic infection. The nitro group of this product is reduced to an amino group in an anaerobic environment to show an anti-anaerobic effect, but it is not effective for aerobic or facultative aerobic bacteria. It has good antibacterial effect on the following anaerobic bacteria: Bacteroides, including Bacteroides fragile; Clostridium; Clostridium, including tetanus; some Eubacteria; digestive cocci and digestion Streptococcus and so on. Oral absorption is good (> 80%). Oral 250mg or 500mg, peak serum drug concentration in 1 ~ 2 hours, 6g / ml and 12g / ml, respectively. Intravenous infusion of 15mg / kg, and then infusion of 7.5mg / kg every 6 hours, when the plasma drug concentration reached steady state, the peak concentration was 25g / ml, and the trough concentration was 18g / ml. This product is widely distributed in the body. It can enter saliva, breast milk, liver abscess pus, and cerebrospinal fluid (the concentration in normal human cerebrospinal fluid can reach 50% of blood). In the body, it is metabolized by side chain oxidation or combined with glucuronic acid, and 20% of drugs are not metabolized. Its metabolites also have some activity. Metronidazole and its metabolites are largely excreted by urine (60% to 80% of the total), and small amounts are excreted by feces (6% to 15%). t1 / 2 is about 8 hours.

Metronidazole indications

It is mainly used to treat or prevent systemic or local infections caused by the above anaerobic bacteria, such as anaerobic infections in the abdominal cavity, digestive tract, female reproductive system, lower respiratory tract, skin and soft tissues, bones and joints, etc. Meningitis, meningeal infections, and colitis caused by antibiotics are also effective. Tetanus is often used in combination with tetanus antitoxin (TAT). Can also be used for oral anaerobic infections.

Metronidazole usage and dosage

Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.

Metronidazole adverse reactions

The most common gastrointestinal reactions include nausea, vomiting, loss of appetite, abdominal cramps, and generally do not affect treatment; neurological symptoms include headache, dizziness, occasional paresthesia, limb numbness, ataxia, polyneuritis, etc. Dose can cause convulsions. A few cases of urticaria, flushing, pruritus, cystitis, dysuria, metal taste in the mouth, and decreased white blood cells are reversible, and they will recover on their own.

Metronidazole contraindications

Patients with active central nervous system disorders and hematological disorders are prohibited. Banned during pregnancy and lactation.

Metronidazole precautions

(1) Drugs can accumulate in patients with liver dysfunction through liver metabolism and should be reduced as appropriate. (2) The sodium salt intake should be reduced during application. If too much salt can cause sodium retention. (3) Can induce candidiasis, if necessary, can be combined with anti-candidiasis drugs. (4) It can cause peripheral neuritis and convulsions. In this case, drug withdrawal (or reduction) should be considered. (5) It can cause changes in blood image and leukopenia, etc., so it should be paid attention to. The metabolites of this product can make the urine appear dark red.

Metronidazole drug interactions

(1) This product can slow the metabolism of oral anticoagulants (such as warfarin, etc.), and strengthen its effect, so that prothrombin time is prolonged. (2) Cimetidine and other liver enzyme inducers can accelerate the elimination of this product and reduce its effectiveness. (3) This product can inhibit acetaldehyde dehydrogenase, so it can strengthen the effect of ethanol, leading to disulfide wake reaction. During medication and within 1 week after discontinuation, alcohol-containing beverages or medicines are prohibited.

Metronidazole preparations

Tablets: 0.2g each. Injection: 50mg (10ml); 100mg (20ml); 500mg (100ml); 1.25g (250ml); 500mg (250ml). Metronidazole glucose injection: 250ml, containing 0.5g of metronidazole and 12.5g of glucose. Suppositories: 0.5g each; 1g. Rectal administration, 0.5g once, 1.5g per day. Metronidazole vaginal effervescent tablets: 0.2g each. Vaginal administration, 0.2 ~ 0.4g once, 7 days as a course of treatment ^[3-6] .