What Is Trimethoprim?

Trimethoprim, English / Latin name: Trimethoprim, TMP for short. This product is white or off-white crystalline powder; odorless and bitter. This product is slightly soluble in chloroform, slightly soluble in ethanol or acetone, almost insoluble in water; easily soluble in glacial acetic acid. This product has a melting point of 199 ~ 203 ° C, molecular formula: C14H18N4O3, molecular weight: 290.31800, and absorption coefficient is 198 ~ 210. Trimethoprim is a synthetic broad-spectrum antibacterial agent. It is used alone for respiratory infections, urinary tract infections, intestinal infections and other diseases. Bacteria), etc. Trimethoprim combined with sulfa-2,6-dimethoxypyrimidine can also be used to treat chloroquine-resistant malaria. [1-2]

Trimethoprim, English / Latin name: Trimethoprim, TMP for short. This product is white or off-white crystalline powder; odorless and bitter. This product is slightly soluble in chloroform, slightly soluble in ethanol or acetone, almost insoluble in water; easily soluble in glacial acetic acid. This product has a melting point of 199 to 203 ° C, a molecular formula: C14H18N4O3, a molecular weight: 290.31800, and an absorption coefficient of 198 to 210. Trimethoprim is a synthetic broad-spectrum antibacterial agent. It is used alone for respiratory infections, urinary tract infections, intestinal infections and other diseases. Bacteria), etc. Trimethoprim combined with sulfa-2,6-dimethoxypyrimidine can also be used to treat chloroquine-resistant malaria. [1-2]
Drug Name
Trimethoprim
Alias
Sulfonamide synergist; trimethoprim; trimethoprim; trimethoprim
Foreign name
Trimethoprim
Main indications
Urine infections, prostatitis, etc. caused by sensitive bacteria
Dosage
See below for details
Adverse reactions
Allergic reactions, gastrointestinal reactions, etc.
Main medication contraindications
Not suitable for premature infants and newborns
Dosage form
Tablets, injections
Drug type
chemical
CAS number
738-70-5

Trimethoprim Basic Information

Chinese name: Trimethoprim
Chinese alias: methoxybenzylpyrimidine; trimethoprim Diamine; antibacterial synergist
English name: trimethoprim
English alias: trimethoprim crystalline; 5- (3,4,5-trimethoxybenzyl) pyrimidine-2,4-diyldiamine; Antibiotic synergist
CAS number: 738-70-5 [1]
EINECS number: 212-006-2
Molecular formula: C14H18N4O3
Molecular weight: 290.32
Chemical Structure:
Exact mass: 290.13800
PSA: 105.51000
LogP: 2.42000

Trimethoprim physical and chemical properties

Appearance and properties: white to light yellow powder
Density: 1.252 g / cm3
Melting point: 199-203 ° C
Boiling point: 526ºC at 760 mmHg
Flash point: 271.9ºC
Stability: Stable. Incompatible with strong oxidizing agents, acids.
Storage conditions: 2-8ºC [1]

Trimethoprim Safety Information

Packing level: III
Hazard category: 6.1 (b)
Customs code: 2933599090
Dangerous Goods Transport Code: 3249
WGK Germany: 3
Danger category code: R25
Safety instructions: S45
RTECS number: UV8225000
Dangerous goods mark: T [1]

Trimethoprim production method

Can be synthesized from gallic acid and guanidine nitrate. [1]

Trimethoprim Pharmacopoeia Standard

Trimethoprim

Chinese name: trimethoprim
Phonetic script (Hanyu Pinyin): Jiayang Bianding
English name: Trimethoprim

Trimethoprim molecular formula and molecular weight

C14H18N4O3 290.32

Trimethoprim source (name), content (potency)

This product is 5-[(3,4,5-trimethoxyphenyl) methyl] -2,4-pyrimidinediamine. Calculated on dry basis, containing C14H18N4O3 shall not be less than 99.0%.

Trimethoprim traits

This product is white or off-white crystalline powder; odorless and bitter.
This product is slightly soluble in chloroform, slightly soluble in ethanol or acetone, almost insoluble in water; easily soluble in glacial acetic acid.
Melting point
The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 199 to 203 ° C.
Absorption coefficient
Take this product, weigh it precisely, add dilute acetic acid to dissolve and quantitatively dilute to make a solution containing about 100g per 1ml, and then add water to quantitatively dilute to make a solution containing about 20g per 1ml. According to ultraviolet-visible spectrophotometry (Appendix IVA of Pharmacopoeia Part II of the 2010 edition), the absorbance was measured at a wavelength of 271 nm, and the absorption coefficient () was 198 to 210. [3]

Trimethoprim identification

(1) Take about 20mg of this product, add 2ml of dilute sulfuric acid to dissolve, add 2 drops of iodine test solution, and a brown precipitate will be formed.
(2) Take 20mg of this product, weigh it accurately, add 5ml of ethanol to dissolve, and add 0.4% sodium hydroxide solution to make a solution containing 20g per 1ml. According to ultraviolet-visible spectrophotometry (Appendix IV A of Part Two of the Pharmacopoeia 2010), it has the maximum absorption at a wavelength of 287 nm, and its absorbance is about 0.49.
(3) The infrared light absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Drugs" 103). [3]

Trimethoprim test

Alkalinity
Take 0.50g of this product, add 50ml of water, shake, and filter. Take the filtrate and determine it according to the law (Appendix VI H of the Pharmacopoeia of the 2010 edition), the pH value should be 7.5 ~ 8.5.
Clarity and color of acid solutions
Take 1.0g of this product and add 25ml of acetic acid to dissolve. The solution should be clear and colorless; if color is developed, compare with the control solution (take the yellow colorimetric standard coloring solution and mix it with the same amount of water) (2010 edition Pharmacopoeia II (Appendix A), must not be deeper. relative substance
Take about 50mg of this product, put it in a 50ml measuring bottle, add the appropriate amount of mobile phase, shake to dissolve, dilute to the mark with the mobile phase, shake well, and use it as the test solution; take an appropriate amount of the precise amount and dilute with mobile phase to make each As a control solution, 2 ml of the solution was contained in 1 ml. Tested according to high-performance liquid chromatography (Appendix VD of Part Two of the Pharmacopoeia, 2010 edition), using octadecylsilane bonded silica as a filler; acetonitrile-water-triethylamine (200: 799: 1) (using sodium hydroxide The test solution or glacial acetic acid was adjusted to pH 6.4) as the mobile phase; the detection wavelength was 280 nm. Take appropriate amounts of trimethoprim reference substance and dimethoxybenzidine reference substance, dissolve and dilute with mobile phase to make a solution containing 2g of trimethoprim and 1g of dimethoxybenzidine per 1ml, as a system suitability test Take 20l of the solution and inject it into the liquid chromatograph. Adjust the detection sensitivity so that the peak height of the trimethoprim chromatographic peak is about 20% of the full scale. The theoretical plate number is not less than 5000 based on the trimethoprim peak. The resolution of the pyrimidine peak from the dimethoxypyridine peak should be greater than 2.5. Precisely measure 20 l each of the test solution and the control solution, and inject them into the liquid chromatograph respectively, and record the chromatogram to 4 times the peak retention time of the main component. If there is an impurity peak 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 (0.2%), and the sum of the areas of the impurity peaks must not be more than twice the area of the main peak of the control solution (0.4%). Any peaks smaller than 0.05 times the main peak area of the control solution in the chromatogram of the test solution are ignored. [3]
Loss on drying
Take this product and dry it at 105 to constant weight, and the weight loss shall not exceed 0.5% (Appendix L of Part Two of the Pharmacopoeia of 2010 Edition).
Residue on ignition
Must not exceed 0.1% (Appendix N of Part Two of the 2010 Pharmacopoeia).

Determination of trimethoprim

Take about 0.2g of this product, accurately weigh, add 20ml of glacial acetic acid, warm to dissolve, let cool, add 1 drop of crystal violet indicator solution, titrate with perchloric acid titrant (0.1mol / L) until the solution becomes blue And correct the titration results with a blank test. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 29.03mg of C14H18N4O3. [3]

Trimethoprim category

Antibacterials.

Trimethoprim storage

Shaded and sealed.

Trimethoprim

(1) Trimethoprim tablets (2) Trimethoprim injection

Overview of trimethoprim- related information

Trimethoprim drug name

Chinese name: trimethoprim
English name: Trimethoprime
Alias: Sulfa synergist; Trimethoprim; Trimethoprim; Trimethoprim; TMP; Trimethoprime; Trimethoprimum

Trimethoprim classification

Antibiotics> Sulfa

Trimethoprim dosage form

1. Tablets: 0.1g each;
2. Injection: 2ml: 0.1g.

Trimethoprim pharmacological effects

Trimethoprim is a bacterial dihydrofolate reductase inhibitor and a sulfa potentiator. Its antibacterial action principle is to interfere with the folate metabolism of bacteria. It is mainly to selectively inhibit the activity of dihydrofolate reductase of bacteria, so that dihydrofolate cannot be reduced to tetrahydrofolate, thereby inhibiting the growth and reproduction of bacteria. Trimethoprim has antibacterial activity against most Gram-positive and Gram-negative bacteria. In addition, trimethoprim has certain effects on Plasmodium and certain fungi, such as nocardia, histoplasma, and yeast. Among Gram-positive bacteria, Streptococcus pneumoniae-containing Streptococcus is sensitive to trimethoprim. Among Gram-negative bacteria, E. coli, Salmonella, Proteus mirabilis, Pneumococcus, Shigella, Typhoid, Pertussis, etc. are sensitive to trimethoprim. Trimethoprim has no antibacterial effect on Pseudomonas aeruginosa, meningococci, and Alcaligenes. [2]

Trimethoprim pharmacokinetics

Trimethoprim is completely absorbed after oral administration, and can absorb more than 90% of the dose. Oral 0.1g, peak blood concentration after 1 to 4 hours, about 1mg / ml. The apparent volume of trimethoprim is 1.2-2.2L / kg. The drug is widely distributed in tissues and body fluids after absorption, and its concentration in kidney, liver, spleen, lung, muscle, bronchial secretion, saliva, vaginal secretion, prostate tissue and prostate fluid exceeds plasma concentration. Trimethoprim can penetrate the blood-cerebrospinal fluid barrier into the cerebrospinal fluid. The cerebrospinal fluid drug concentration in the absence of inflammation of the meninges is 30% to 50% of the blood concentration, and it can reach 50% to 100% when there is inflammation. Trimethoprim can also penetrate the blood-placental barrier, and the drug concentration in fetal blood circulation is similar to that of maternal blood. The trimethoprim concentration in milk is close to or higher than the blood drug concentration, and the drug concentration in aqueous humor is about 1/3 of the blood drug concentration. The trimethoprim protein binding rate is 30% to 46%. The elimination half-life is about 8-10 hours, and the half-life of those without urine can be extended to 20-50 hours. The drug is mainly filtered through the glomerulus, and the renal tubules are excreted with urine. In 24 hours, about 50% to 60% of the dose can be excreted, of which 80% to 90% are excreted in the form of the drug, and the rest are excreted in the form of metabolites. The average urine concentration is 90 to 100 mg / L, and the peak urine concentration is about 200 mg / L. A small amount of medicine (about 4% of the dose) can be excreted from bile and feces. Trimethoprim can be removed by hemodialysis, but not by peritoneal dialysis. [2]

Trimethoprim indication

1. Trimethoprim can be used alone to treat acute simple urinary tract infection and bacterial prostatitis caused by sensitive bacteria.
2. Trimethoprim combined with sulfamethoxazole or sulfadiazine can be used to treat septicemia, meningitis, otitis media, typhoid fever, shigellosis (bacillary dysentery) caused by sensitive bacteria.
3. Trimethoprim combined with sulfa-2,6-dimethoxypyrimidine can also be used to treat chloroquine-resistant malaria. [2]

Trimethoprim contraindications

Trimethoprim should not be used in preterm infants and newborns. [2]

Trimethoprim notes

1. (1) People with impaired liver function; (2) People with impaired renal function; (3) Patients with megaloblastic anemia or other blood system diseases caused by folate deficiency.
2. The effects of drugs on breastfeeding: Trimethoprim can be secreted into breast milk, and its concentration is high, and the drug may interfere with the folate metabolism of nursing infants. Therefore, lactating women must weigh the pros and cons before deciding whether to take medication.
3. Periodic blood examinations should be performed regularly during medication. [2]

Trimethoprim pregnancy classification

FDA pregnancy classification: C [4]

Trimethoprim lactation grading

Trimethoprim: L2, half-life 8-10h Because it can interfere with folic acid metabolism, long-term use should be avoided or supplemented with folic acid for infants [4]

Trimethoprim adverse reactions

1. Leukopenia, thrombocytopenia, or hemoglobin anemia may occur.
2. Allergic reactions: skin itching, rash, and occasionally severe exudative polymorphic erythema.
3. Gastrointestinal reaction: nausea, vomiting, diarrhea, and other gastrointestinal symptoms can occur, and the general symptoms are mild.
4. Liver toxicity: occasional liver dysfunction.
5. Other: Aseptic meningitis may occur, and symptoms such as headache and neck stiffness may occur. [2]

Trimethoprim dosage

1. (1) Acute simple urinary tract infection: 0.1g each time, once every 12 hours; or 0.2g each time, once a day. The course of treatment is 7 to 10 days. (2) Prevention of urinary tract infection: 0.1g each time, once a day.
2. Dose at renal insufficiency: Those with impaired renal function need to adjust the dose according to creatinine clearance. If the creatinine clearance rate is greater than 30ml per minute, the amount commonly used by adults is used. If the creatinine clearance rate is 15-30ml per minute, take 50mg every 12 hours. If the creatinine clearance rate is less than 15ml per minute, trimethoprim should not be used. [2]
3. Dose during dialysis: Trimethoprim can be removed by hemodialysis, and a maintenance dose needs to be replenished after hemodialysis. [2]

Interaction of trimethoprim with other drugs

1. Trimethoprim combined with sulfa drugs can double-block the folic acid anabolic metabolism of bacteria, have a synergistic antibacterial effect, and turn its antibacterial effect into a bactericidal effect.
2. Trimethoprim and berberine, oxytetracycline, ampicillin, gentamicin, kanamycin, amikacin, lincomycin, and fosfomycin have significant synergistic effects .
3. Trimethoprim combined with polymyxin and kasugamycin can achieve 2-32 times synergistic effect.
4. The combination of trimethoprim, pyridinic acid, and norfloxacin has a significant synergistic effect, and the adverse drug reactions are also lower than the single medication.
5. Trimethoprim combined with cefadroxil can enhance the efficacy and delay the development of bacterial resistance.
6. The use of dapsone and trimethoprim can increase the blood concentration of both, and the rise of dapsone can increase the adverse reactions and worsen, especially the occurrence of methaemoglobinemia. [2]
7. Trimethoprim can interfere with the intrahepatic metabolism of phenytoin, increase the serum half-life of phenytoin by 50%, and reduce its clearance by 30%.
8. Trimethoprim and procainamide can reduce renal clearance.
9. Trimethoprim with warfarin can inhibit the metabolism of warfarin and enhance its anticoagulant effect.
10. Trimethoprim and cyclosporine can increase renal toxicity.
11. The combined use of bone marrow inhibitors and trimethoprim may increase the chance of leukocytes and thrombocytopenia.
12. Trimethoprim is used in combination with antitumor drugs and 2,4-diaminopyrimidine drugs, which may cause bone marrow agenesis or megaloblastic anemia.
13. Trimethoprim with rifampicin can increase trimethoprim clearance and shorten serum half-life. [2]

Trimethoprim Expert Reviews

Trimethoprim's antibacterial spectrum is similar to that of sulfamethoxazole and isoxazole, and its antibacterial effect is 20 to 100 times stronger than that of sulfamethoxazole and isoxazole. Medicinal, mostly combined with sulfa drugs. Trimethoprim is a bacteriostatic drug when used alone, and when used in combination with sulfa drugs, it is synergistic and can even kill bacteria. If the bacteria are sensitive to these two drugs when used alone, the subinhibitory concentration of one drug can reduce the MIC of the other drug by more than 4 to 8 times. But the synergism is different in different bacteria or strains. There is a high degree of synergy between Neisseria gonorrhoeae and Proteus. In most staphylococci, streptococci, pneumococci, and influenza bacilli only synergize 4-8 times. The concentration that produced the greatest synergy was the respective MIC combination. There are also some strains that are sensitive to both drugs but do not produce a synergistic effect. For example, bacteria are resistant to sulfa drugs and only sensitive to trimethoprim. Generally speaking, synergy cannot be generated, which is equivalent to TMP alone. For example, if the concentration of sulfa drugs is high, synergy can occur in vitro. This is of little clinical significance, because it is not safe to use too much sulfa drug, but it may be beneficial for urinary tract infections, because sulfa drugs are high in urine. For example, Pseudomonas aeruginosa is moderately resistant to sulfa drugs and may have a synergistic antibacterial effect when combined with trimethoprim. Domestic studies have proven that trimethoprim has a synergistic effect on various antibiotics. For example, the combined effect of tetracycline on Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa is greater than that on sulfamethoxazole; on drug-resistant Staphylococcus, trimethoprim can enhance penicillin and neopenicillin and erythromycin; can enhance the effect of gentamicin and kanamycin on Pseudomonas aeruginosa. However, some people think that trimethoprim should not be used in combination with tetracycline, doxycycline, kanamycin or gentamicin because very few strains produce synergistic effects. Trimethoprim has been reported to have significant synergistic effects abroad, including Streptococcus pyogenes, Enterococcus, Proteus, Klebsiella, E. coli, and Pseudomonas aeruginosa. Animal experiments have also been shown to improve survival in infected mice. Resistant strains of rifampicin or trimethoprim can also be synergistic. The commonly used amounts of the two drugs can reach a synergistic level in patients. Sulfa drugs and polymyxins have a synergistic effect on negative bacilli. Addition of trimethoprim is even better. The resistance of trimethoprim to bacterial resistance during treatment is currently uncommon, about 10%. This may be because TMP is often used in combination with sulfa drugs, and pathogens that are sensitive to both drugs are not prone to develop drug resistance. However, pathogens that are only sensitive to TMP are prone to drug resistance. It has also been proven in the laboratory that the resistance of negative bacteria to TMP has developed rapidly, and clinical resistance will increase over time. [2]

Trimethoprim complex

Trimethoprim pharmacological effects

This strain is a compound preparation of sulfamethoxazole (SMZ), sulfadiazine (SD) and trimethoprim (TMP). It has a broad antibacterial spectrum, strong antibacterial effect, and has a synergistic antibacterial or bactericidal effect on most Gram-positive and negative bacteria, including non-enzyme-producing Staphylococcus aureus, Streptococcus pyogenes, pneumococcus, Escherichia coli, gram Enterobacteriaceae bacteria such as R. spp., Salmonella, Proteus, M. spp., Shigella, etc., gonococci, meningococcus, Haemophilus influenza, etc. all have good antibacterial activity. Drug resistance is widespread, especially bacteria of the Enterobacteriaceae family, such as Shigella, so it is rarely used clinically. In addition, it has good antibacterial activity against Vibrio cholerae and Chlamydia trachomatis in vitro. Its mechanism of action is that both SMZ and SD can compete with paraaminobenzoic acid for dihydrofolate synthase, preventing bacteria from synthesizing dihydrofolate, and TMP inhibits the reduction of dihydrofolate to tetrahydrofolate by inhibiting the bacteria's dihydrofolate reductase. . When the three are used together, it has a double blocking effect on the tetrahydrofolate synthesis by bacteria, and its antibacterial effect is enhanced compared to that of a single drug, and the strains showing resistance to it are correspondingly reduced. The product is a white tablet.

Trimethoprim kinetics

The product is absorbed from the gastrointestinal tract after oral administration, and is widely distributed in systemic tissues and fluids. Easy to penetrate the blood-brain barrier and placental barrier. This product is mainly metabolized by the kidneys.

Trimethoprim indications

It is mainly used for urinary tract infections, intestinal infections, acute episodes of chronic bronchitis in adults, acute otitis media, etc. caused by bacteria sensitive to this product.

Trimethoprim dosage

The usual dosage for oral adults is: 2 tablets at a time, twice a day, and the first dose is doubled. The course of acute exacerbation of chronic bronchitis is at least 10 to 14 days; the course of urinary tract infection is 7 to 10 days; bacterial dysentery 5 to 7 days; and acute otitis media is 10 days.

Trimethoprim adverse reactions

1. Allergic reactions are more common. It can manifest as drug eruption, exudative erythema polymorpha, exfoliative dermatitis, and bullous epidermal atrophic dermatitis can occur in severe cases; it can also manifest as photosensitivity, drug fever, joints and muscle
Adverse reactions-jaundice
Pain, fever and other serum sickness-like reactions. Occasional anaphylactic shock.
2, neutropenia or deficiency, thrombocytopenia, and occasionally aplastic anemia. Patients can show sore throat, fever, and bleeding tendency.
3. Hemolytic anemia and hemoglobinuria. This is prone to occur in patients lacking glucose-6-phosphate dehydrogenase after application of sulfa drugs, and is more common in neonates and children than adults.
4. Hyperbilirubinemia and nuclear jaundice in newborns. Because the product competes with bilirubin for protein binding sites, it can cause increased free bilirubin. Newborn liver function is imperfect, so it is more prone to hyperbilirubinemia and neonatal jaundice, and nuclear jaundice may occur occasionally.
5. Liver damage. Jaundice and liver failure may occur, and acute liver necrosis may occur in severe cases.
6, kidney damage. Crystalline urine, hematuria, and cast urine can occur; occasional patients have severe adverse reactions such as interstitial nephritis or renal tubular necrosis.
7, nausea, vomiting, decreased appetite, diarrhea, headache, fatigue, etc. General symptoms are mild and do not affect continued medication. Occasionally, C. difficile enteritis occurs and the drug needs to be discontinued at this time.
8. Goiter and hypofunction occur occasionally.
9. Central nervous system toxicity can occur occasionally, manifested as insanity, disorientation, hallucinations, euphoria, or depression, and should be discontinued immediately.
10. Due to the interference of TMP on folic acid metabolism, adverse reactions in the blood system can occur, and leukopenia, thrombocytopenia, or methemoglobinemia can occur. Leukopenia and thrombocytopenia are generally mild.
11, occasionally aseptic meningitis, headache, neck stiffness, nausea and other manifestations. Although serious adverse reactions caused by this product are rare, they often involve various organs and can be fatal, such as exudative erythema multiforme, exfoliative dermatitis, bullous epidermal atrophic dermatitis, fulminant liver necrosis, and agranulocytosis And abnormal blood systems such as aplastic anemia.

Trimethoprim is contraindicated

1. Those who are allergic to sulfa drugs are prohibited.
2. As the product prevents the metabolism of folic acid and aggravates the deficiency of folate in patients with megaloblastic anemia, the patient is prohibited from using the product.
3, pregnant women and lactating women are prohibited from using this product.
4. This product is forbidden for infants less than 2 months old.
5. Those with impaired liver and kidney function should not use this product.

Trimethoprim notes

1. Cross-allergic reactions. Patients who are allergic to one sulfa drug may also be allergic to other sulfa drugs.
2. Liver damage. Jaundice and liver failure may occur, and acute liver necrosis may occur in severe cases. Therefore, patients with liver damage should avoid systemic application of sulfa drugs.
3. Kidney damage. Crystalline urine, hematuria, and cast urine can occur. If the product is used for a long course of treatment, it is advisable to take sodium bicarbonate and drink more water when the dose is large. To prevent this adverse reaction. During the treatment, check the urine routine at least 2 to 3 times a week. If you find crystalline urine or hematuria, give sodium bicarbonate and drink plenty of water until the crystalline urine and hematuria disappear. Dehydration, shock, and elderly patients are prone to kidney damage when using this product, and should be used with caution or avoidance. This product should not be used in patients with impaired renal function.
4. Patients who are allergic to furosemide, sulfones, thiazines, diuretics, sulfonylureas, and carbonic anhydrase inhibitors can also be allergic to sulfa drugs.
5. The following conditions should be used with caution: lack of glucose-6-phosphate dehydrogenase, hematoporphyria, folic acid deficient blood system diseases, dehydration, AIDS, shock and elderly patients.
6. Please pay attention during the medication: peripheral blood examination is particularly important for patients with long treatment courses, large doses, old age, malnutrition and taking antiepileptic drugs. Regular urinalysis during the treatment (check the urine routine every 2-3 days) to find the crystallized urine that may occur during long courses or high-dose treatments. liver and kidney function tests.
7. Drink plenty of water every time you take this product. Sufficient water intake should also be maintained during taking, so that the urine output of adults is maintained at least 1200ml per day. If the product is used for a long course of treatment, a large dose of sodium bicarbonate should be taken in addition to drinking plenty of water.
8. The blood drug concentration should be measured in severely infected patients, and it can be effective for most patients with infectious diseases whose free sulfonamide concentration reaches 50-150 g / ml (severe infection 120-150 g / ml). The total blood sulfonamide concentration should not exceed 200 g / ml. If this concentration is exceeded, the incidence of adverse reactions will increase.
9. Do not arbitrarily increase the dose, increase the number of medications or extend the course of treatment to prevent accumulation of poisoning.
10. As the product can inhibit the growth of E. coli and hinder the synthesis of B vitamins in the intestine, those who use the product for more than a week should be given vitamin B at the same time to prevent its deficiency.
11. If folic acid deficiency is caused by taking this product, you can also take folic acid preparations at the same time, the latter does not interfere with the antibacterial activity of TMP, because the bacteria can not use the synthesized folic acid, if there is a sign of bone marrow suppression, it should be stopped immediately And give 3 to 6 mg of folic acid intramuscularly once a day for 2 days or as needed until the hematopoietic function returns to normal. For long-term and excessive use of this product can be given high doses of folic acid and prolong the course of treatment.
12. Because sulfa drugs can compete with bilirubin for binding sites on plasma proteins, and the neonatal acetyltransferase system is not fully developed, the free blood concentration of sulfa is increased, which increases the risk of nuclear jaundice. The use of the drug in newborns and infants under 2 months is contraindicated. 1. Sulfa drugs can cross the blood placental barrier to the fetus. Animal experiments have found teratogenic effects. Human research lacks sufficient information, and pregnant women should avoid using it. 2. Sulfonamides can be secreted from breast milk. The concentration in breast milk can reach 50% to 100% of the blood concentration of the mother. The drug may affect the baby. Sulfonamides are used in newborns with glucose-6-phosphate dehydrogenase deficiency. The application may lead to the occurrence of hemolytic anemia. In view of the above reasons, lactating women have suspended the application of this product. Elderly patients have an increased chance of serious adverse reactions when using sulfa drugs. Such as severe rash, bone marrow suppression and thrombocytopenia. Therefore, it should be avoided in elderly patients, and the pros and cons should be weighed when there are indications.

Trimethoprim overdose

The blood concentration of sulfa should not exceed 200 g / ml. Above this concentration, the incidence of adverse reactions increases and the toxicity increases. Excessive short-term use of this product will cause loss of appetite, abdominal pain, nausea, vomiting, and dizziness
Severe drug eruption
, Headache, drowsiness, unconsciousness, depression, fever, hematuria, crystal urine, blood disease, jaundice, bone marrow suppression, etc. Long-term overdose of this product will cause bone marrow suppression, resulting in reduction of platelets, white blood cells and megaloblastic anemia.

Trimethoprim interaction

1. Combined use of urinary alkalizing drugs can increase the solubility of the product in alkaline urine and increase excretion.
2. It cannot be combined with para-aminobenzoic acid. Para-aminobenzoic acid can be taken up by bacteria instead of the product, and the two antagonize each other.
3. When the following drugs are used together with this product, this product can replace the protein binding site of these drugs, or inhibit their metabolism, so that the drug action time is prolonged or a toxic reaction occurs. Therefore, when these drugs are used at the same time as this product, or when the product is used The dosage needs to be adjusted when the product is used later. Such drugs include oral anticoagulants, oral hypoglycemic agents, methotrexate, phenytoin, and thiopental.
4. Combination with bone marrow inhibitory drugs may enhance the adverse reactions of these drugs to the hematopoietic system. Such as leukocytes, thrombocytopenia, etc., if there are indications that both drugs are used together, the possible toxic reactions should be closely observed.
5. Long-term combination with contraceptives (estrogen) can reduce the reliability of contraception and increase the chance of extramenstrual bleeding.
6. When combined with thrombolytic drugs, their potential toxic effects may be increased.
7. When combined with hepatotoxic drugs, it may cause an increase in the incidence of hepatotoxicity. Liver function should be monitored in such patients, especially those who have been taking the drug for a long time and have a previous history of liver disease.
8. When combined with photosensitizing drugs, the addition of photosensitivity may occur.
9. The requirement of vitamin K for those who received this product increased.
10. It should not be used in combination with urotropine, because urotropine can be decomposed in acid urine to produce formaldehyde, which can form an insoluble precipitate with the product. Increases the risk of crystallized urine.
11. This product can replace the plasma protein binding site of Baotaisong. When both are used together, it can enhance the effect of Baotaisong.
12, sulfinpyrazone (sulfinpyrazone) when combined with this product can reduce the secretion of the latter from the renal tubules, its blood concentration is increased and lasting, resulting in toxic reactions, so during the application of sulfinpyrazone or after treatment The dose of this product may need to be adjusted. When the duration of the treatment with sulfopyridone is long, the blood concentration of the product should be monitored to help adjust the dose and ensure safe medication.
13. TMP in this product can inhibit the metabolism of warfarin and enhance its anticoagulant effect.
14. The combination of TMP and cyclosporine in this product can increase renal toxicity.
15. When rifampicin is used in combination with this product, it can obviously increase the clearance of TMP in this product and shorten the serum half-life.
16. It should not be used in combination with antitumor drugs and 2,4-diaminopyrimidine drugs, and it should not be used between the courses of treatment with other folic acid antagonists, because there may be the possibility of poor bone marrow regeneration or megaloblastic anemia.
17. It should not be used in combination with dapsone. Both dapsone and TMP in this product can increase the blood concentration. The rise in dapsone concentration increases the adverse reactions and worsens, especially methemoglobinemia. happened.
18. Avoid combination with penicillin drugs, because this product may interfere with the bactericidal effect of such drugs.

Trimethoprim Market Analysis

A large number of low-priced Indian goods hit the market, making Chinese production face severe challenges. Since 1997, the market price of trimethoprim has been declining all the way, and the price per kilogram has gradually dropped from 220 yuan, reaching a minimum of 88 yuan, and the price has fallen by 60%. In recent years, although the prices of chemical raw materials and fuels have risen, trimethoprim prices are still hovering at low prices. Put Chinese production enterprises into a dilemma of no profit or even loss, and the efficiency has seriously deteriorated. During this period, many enterprises stopped production because they could not sustain it. So far, only 3-4 companies in the country are still producing. At the same time, production and export volume have decreased to varying degrees. (
As for the aggressive situation of trimethoprim in India, Chinese companies have not fled. Among them, Shandong Shouguang Fukang Pharmaceutical Co., Ltd. has made a sudden rise in recent years, and its production scale and output have increased significantly year after year. At present, it has occupied half of China's trimethoprim production. In recent years, in the international market, products of trimethoprim in China and India have launched fierce market competition. In recent years, the export volume of trimethoprim in India has dropped a lot compared with before.
Today, the annual production capacity of trimethoprim in China is about 2500 tons and the annual output is about 1,500 tons. The main manufacturers are Shandong Shouguang Fukang Pharmaceutical Co., Ltd., Shandong Xinhua Pharmaceutical Factory, and Southwest Synthetic Pharmaceutical Factory. The annual output and export volume of these companies account for more than 90% of the national total.
The domestic sales of trimethoprim APIs are 800-900 tons per year, which has declined in recent years. Currently it is 500-600 tons. At the end of the 20th century, China's compound Xinnuoming tablet output was 3.2 billion, and now it has reached nearly 4 billion. sheet. At present trimethoprim has been listed as a class A antimicrobial drug in the "National Basic Healthcare Drug Catalog". It is expected that there will still be a broad market space and development potential in China in the future.
In the 21st century, the export volume of trimethoprim in China has risen again, currently about 800 tons. The main export companies are Shandong Shouguang Fukang Pharmaceutical Company, Southwest Synthetic Pharmaceutical Factory, Shandong Xinhua Pharmaceutical Factory, etc., but the export prices are relatively low. Southwest Synthetic Pharmaceutical Factory is currently in a situation of providing exclusive sales to some major foreign customers because its products have obtained the European COS certificate and the US FDA certification, and have large fixed customers for export, and the prices are ideal.
So far, trimethoprim has been widely used as a new force for anti-infective drugs in the majority of third world countries, and it is mainly used in veterinary medicine in developed countries. Now the world s annual consumption is nearly 10,000 tons. In recent years, people have found that the combined application of trimethoprim and other antibacterial drugs can also greatly improve the antibacterial effect. With the continuous research in this area, it is believed that its market development space will be greatly expanded.

The future development of trimethoprim

1. Stabilize production and strengthen coordination. In the future, trimethoprim will still maintain a certain share in the Chinese pharmaceutical market, and sales will rise steadily. In addition to the export of foreign trade, China's trimethoprim output should be kept at 1,500-2,000 tons during the tenth year. Now the production of trimethoprim in China has been concentrated in a few large factories, and economies of scale have taken shape. The annual production capacity of the four major production plants has reached 1,500 tons, and the product quality and technical level are relatively similar, which can fully meet the needs of the domestic market and foreign trade exports. In order to achieve sustained and healthy development of trimethoprim, it is not appropriate to build new production sites. The major production enterprises should strengthen ties, coordinate with each other, control the total amount according to market demand, stabilize prices, and improve economic efficiency.
2. Expand exports and open up markets. Trimethoprim, as an old anti-infective drug variety, has its own advantages and characteristics, and it is expected that there will be greater demand in the international market in the future. An important reason for the rapid growth of India's bulk drug exports is the support of its government's many preferential policies. Relevant national departments should also adopt more active preferential policies based on surveys to encourage the export of Chinese medicines such as trimethoprim.
3. Continuous innovation and development of new products. The combination of trimethoprim and other antibiotics can better exert the effect of antibiotics, especially the most obvious synergistic effect on tetracycline and gentamicin, which can be enhanced by more than ten times. Therefore, in recent years, new antibiotics and trimethoprim compound preparations have been continuously developed. A few days ago, the Sino-foreign joint venture Kunming Jieda Pharmaceutical Co., Ltd. launched a new compound tablet of cefalexin and trimethoprim to the market. In addition, trimethoprim also has antimalarial effects. In August 2000, a Chinese research institution combined trimethoprim with dihydroartemisinin, piperquine phosphate and other scientific compounds to form a new antimalarial drug-compound dihydro Artemisinin tablets have been approved for clinical research. Domestic enterprises should pay close attention to research progress in this regard, pay attention to information collection, strengthen development research, and introduce better and more compound preparations to the market.

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