What Factors Affect Albendazole Dosage?
Albendazole is a broad-spectrum intestinal anthelmintic drug of imidazole derivatives. Discovered by GlaxoSmithKline's Animal Health Laboratory in 1972. Albendazole has been included in the World Health Organization's Standard List of Essential Medicines and is one of the most important essential health medicines [1] .
- Drug Name
- Albendazole
- Alias
- Prothiodazole
- Foreign name
- Albendazole
- Main indications
- New highly effective broad-spectrum deworming medicine
- Dosage
- oral
- Dosage form
- tablet
- CASNO
- 54965-21-8
- Molecular formula
- C12H15N3O2S
- Molecular weight
- 265.33
- Albendazole is a broad-spectrum intestinal anthelmintic drug of imidazole derivatives. Discovered by GlaxoSmithKline's Animal Health Laboratory in 1972. Albendazole has been included in the World Health Organization's Standard List of Essential Medicines and is one of the most important essential health medicines [1] .
- Albendazole is a high-efficiency, low-toxicity, broad-spectrum insect repellent. It can be used clinically to drive roundworms, roundworms, roundworms, whipworms, hookworms, and roundworms. After being metabolized into sulfoxides or sulfones in the body, it inhibits the parasite's absorption of glucose, leading to the depletion of the glycogen of the parasite, or inhibits the fumarate reductase system, hinders the production of ATP, and makes the parasite unable to survive and reproduce.
Brief introduction of albendazole compounds
- Chinese name: albendazole
- Chinese alias: 5- (propylthio) -2-benzimidazole carbamic acid methyl ester; prothioimidazole; prothiobenzimidazole; anti-creasity; parasites; intestinal insect clear; albite shike intestinal insect clear; abenzene Daxazole
- English name: albendazole
- English alias: Atasol; ALBENZA; ALBEN; Bilutac; VALBAZEN; ZENTEL; ABENTE; SKF62979
- CAS number: 54965-21-8
- Molecular formula: C 12 H 15 N 3 O 2 S
- Molecular weight: 265.33100
- Exact mass: 265.08800
- PSA: 92.31000
- LogP: 3.31630
- Physical and chemical properties
- Appearance and properties: white to light yellow crystalline powder, odorless
- Melting point: 207-211 ° C (decomposed)
- Water solubility: slightly soluble in organic solvents, insoluble in water
- Storage conditions: 0-6 ° C
- Security Information
- Customs Code: 3004909090
- WGK Germany: 2
- Danger category code: R61; R36 / 37/38
- Safety instructions: S53; S45; S37 / 39; S26
- RTECS number: FD1100000
- Dangerous goods mark: T [1]
- production method
- Method 1: Sodium sulfide was dissolved in 95% ethanol, and 2-nitro-4-thiocyanatoaniline was added at 50 ° C. Stir at 60 ° C, cool to 40 ° C, and add bromopropane in one portion. After the reaction at 40 ° C, the temperature was raised to 60 ° C to react. Add sodium sulfide and react at 80 ° C. The ethanol was distilled off under reduced pressure, and water was added. Cool and extract with chloroform. The extract was washed with water, dried, and S-methyl-N, N-bis (methoxycarbonyl) isothiourea and glacial acetic acid were added and refluxed. The chloroform was distilled off and methanol was added. Cool, suction filter, wash with methanol, and dry to obtain crude albendazole.
- Method 2: While stirring and cooling in an ice bath, slowly add carbendazim to chlorosulfonic acid, keeping the internal temperature of 15-20 ° C. After the addition, stir at 40 ° C. Below 0 ° C, the reaction solution was slowly dropped into 95% ethanol. The precipitate was collected by filtration, washed with a small amount of ethanol, and dried to obtain a chlorosulfonated product with a yield of 90.8%. The chlorosulfonated product was added to a solution of formic acid, water and 40% hydrobromic acid, followed by metal aluminum powder. Stir at 35 40 , and then react at 60 65 . After cooling, it was filtered and the filtrate was adjusted to a Ph value of 3 with 40% sodium hydroxide. The precipitate was collected by filtration, washed, and dried to obtain a mercapto compound with a yield of 82.5%. The mercapto compound was added to an aqueous sodium hydroxide solution to decolorize the activated carbon. Tetrabutylammonium bromide was added, followed by bromopropane in methanol, and the reaction was carried out at 35-40 ° C. After cooling, the precipitate was collected by filtration, washed to neutrality, and dried to obtain albendazole with white crystals, yield 87.5%, melting point 207-209 ° C. Carbendazim was reacted with sodium thiocyanate in the presence of glacial acetic acid. After introducing thiocyanate, it was then reduced with sodium sulfide and reacted with bromopropane to obtain albendazole. Albendazole can be refined by the following methods: crude albendazole (based on dry product) and 85% industrial formic acid (1: 3.5) are stirred and heated to 60 ° C. After the crude product is completely dissolved, sodium dithionite, Activated carbon and EDTA. Continue to stir to warm to 80 ° C. Suction filtration, the filtrate was poured into deionized water, and under stirring with 18% to 20% ammonia in water to a Ph value of 6.5. Suction filtration and drying to obtain a white product, melting point 206 ~ 212 ° C, refined yield of 93% ~ 94% [1] .
- use
- Highly effective broad-spectrum insect repellent. It is a kind of benzimidazole that has a broader insect repellent spectrum and the strongest insecticidal effect. It is suitable for deworming roundworms, roundworms, hookworms and whipworms, treating various types of cysticercosis, and can also be used for deworming of livestock [1] .
Albendazole Pharmacopoeia Standard
Albendazole source (name), content (potency)
- This product is 5- (propylthio) -2-benzimidazole-carbamic acid methyl ester. Calculated on dry basis, containing C12H15N3O2S shall not be less than 98.5%.
Albendazole traits
- This product is white or off-white powder; odorless and tasteless.
- This product is slightly soluble in acetone or chloroform, almost insoluble in ethanol, insoluble in water; soluble in glacial acetic acid.
- Melting point
- The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 206 ~ 212 ° C, and it will decompose at the same time when melting.
- Absorption coefficient
- Take about 10mg of this product, weigh it accurately, place it in a 100ml measuring flask, add 5ml of glacial acetic acid to dissolve, and dilute to the mark with ethanol. According to the UV-Vis spectrophotometry (Appendix IVA of Pharmacopoeia Part II of the 2010 edition), the absorbance was measured at a wavelength of 295 nm, and the absorption coefficient () was 430 to 458.
Albendazole identification
- (1) Take about 0.1g of this product, place the bottom of the test tube, put a wet lead acetate test paper on the mouth of the tube, heat the bottom of the test tube, and the gas generated can make the lead acetate test paper appear black.
- (2) Take about 0.1g of this product, dissolve it in dilute dilute sulfuric acid, and add bismuth potassium iodide test solution dropwise to form a red-brown precipitate.
- (3) Take the solution under the absorption coefficient and measure it by UV-Vis spectrophotometry (Appendix IV A of Part Two of the Pharmacopoeia 2010 Edition). It has the maximum absorption at the wavelength of 295nm and the minimum absorption at the wavelength of 277nm.
- (4) The infrared light absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Drugs" 1092). If it is found that the absorption peak at 1380cm-1 is inconsistent with the control spectrum, take an appropriate amount of this product and dissolve it in absolute ethanol, evaporate it on a water bath, and measure it under reduced pressure.
Albendazole test
- relative substance
- Take this product, add chloroform-glacial acetic acid (9: 1) to dissolve and make a solution containing 10mg per 1ml, as the test solution; take an accurate amount, use chloroform-glacial acetic acid (9: 1) ) Dilute to make solutions containing 100 g and 20 g per 1 ml as control solutions (1) and (2), respectively. According to the thin-layer chromatography method (Appendix VB of Part Two of the Pharmacopoeia, 2010 edition), draw 5 l of each of the three solutions, point them on the same silica gel G thin-layer plate, and use chloroform-ether-glacial acetic acid (30: 7: 3) ) As a developing agent, unfolded, dried, and immediately inspected under an ultraviolet light (254nm). The control solution (2) should show an obvious spot, and the test solution, such as a spot of impurities, should have a fluorescence intensity that is not stronger than the main spot of the control solution (1).
- 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
- Take 1.0g of this product and check it according to law (Appendix N of Part Two of the 2010 Pharmacopoeia). The residual residue shall not exceed 0.2%.
- Iron salt
- Take the residue left under the burning residue, add 2ml of hydrochloric acid, evaporate to dryness in a water bath, add 4ml of dilute hydrochloric acid, dissolve it at a slight temperature, add 30ml of water and 50mg of ammonium persulfate, and check according to law (Appendix G of Part Two of the Pharmacopoeia, 2010 Edition) Compared with the control solution made from 3.0ml of standard iron solution, it must not be deeper (0.003%).
Determination of albendazole
- Take about 0.2g of this product, accurately weigh, add 20ml of glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, titrate with perchloric acid titration solution (0.1mol / L) until the solution becomes green, and use the titration result with Blank test correction. Each 1ml of perchloric acid titration solution (0.1mol / L) is equivalent to 26.53mg of C12H15N3O2S.
Albendazole categories
- Intestinal repellent.
Albendazole storage
- Keep sealed.
Albendazole
- (1) Albendazole tablets (2) Albendazole capsules (3) Albendazole particles
Albendazole Drug Analysis
- Method name: Albendazole API-Determination of Albendazole-Non-aqueous titration
- Scope of application: This method uses titration to determine the content of albendazole in albendazole drug substance.
- This method is applicable to albendazole drug substance.
- Principle of the method: After the test product is dissolved in glacial acetic acid, the crystal violet indicator solution is added, and the solution is titrated with the perchloric acid titration solution until the solution is green. The titration result is corrected by a blank test. Based on the amount of the titration solution, albenda is calculated. Azole content.
- Reagent: 1. Glacial acetic acid
- 2. Perchloric acid titrant (0.1mol / L)
- 3. Crystal violet indicator liquid
- 4. Reference potassium hydrogen phthalate
- equipment:
- Sample preparation: 1. Perchloric acid titration solution (0.1mol / L)
- Preparation: Take 750mL of anhydrous glacial acetic acid (calculated with water content, add 5.22mL of acetic anhydride per 1g of water), add 8.5mL of perchloric acid (70 ~ 72%), shake well, let cool, add an appropriate amount of anhydrous glacial acetic acid 1000mL, shake well and leave for 24 hours. If the test sample is easily acetylated, the water content of the solution must be determined by the moisture measurement method, and then the water content of the solution is adjusted to 0.01% ~ 0.2% with water and acetic anhydride.
- Calibration: Take about 0.16g of standard potassium hydrogen phthalate dried to constant weight at 105 , accurately weigh, add 20mL of anhydrous glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, and slowly titrate with this solution to Blue, and the titration results are corrected with a blank test. Each 1mL of perchloric acid titration solution (0.1mol / L) is equivalent to 20.42mg of potassium hydrogen phthalate. Calculate the concentration of this solution based on the consumption of this solution and the amount of potassium hydrogen phthalate taken.
- Crystal violet indicator liquid
- Take 0.5 g of crystal violet and add 100 mL of glacial acetic acid to dissolve.
- Operation steps: Precisely weigh about 0.2g of the test sample, add 20mL of glacial acetic acid to dissolve, add 1 drop of crystal violet indicator solution, titrate with perchloric acid titrant (0.1mol / L) until the solution becomes green, and The results were corrected with a blank test. Each 1mL of perchloric acid titration solution (0.1mol / L) is equivalent to 26.53mg of C12H15N3O2S.
- Note: "Precision weighing" means that the weighed weight should be accurate to one thousandth of the weighed weight. "Precision measurement" means that the accuracy of measuring the volume should meet the accuracy requirements of the volume pipette in national standards [2] .
Albendazole Drug Description
Albendazole Pharmacology and Toxicology
- Albendazole is a benzimidazole derivative, which is rapidly metabolized to sulfoxide, sulfone alcohol, and 2-aminosulfone alcohol in the body. Selectively and irreversibly inhibits the polymerization of the cytoplasmic microtubule system of intestinal parietal cells of the intestinal nematode, blocking its uptake and absorption of various nutrients and glucose, leading to the depletion of endogenous glycogen and inhibiting fumaric acid reduction The enzyme system prevents the production of adenosine triphosphate, which makes the insect body unable to survive and reproduce. Similar to mebendazole, this product can also cause cytoplasmic microtubule degeneration of intestinal cells of the worm body, and bind to its tubulin, causing blockage of intracellular transportation, causing the accumulation of Golgi endocrine particles, cytoplasm gradually dissolving, and absorption cells completely degenerating. Causes worm death. This product has the functions of completely killing hookworm eggs and whipworm eggs and partially killing roundworm eggs. In addition to killing and repelling various nematodes parasitic in animals, it also has obvious killing and repellent effects on roundworms and cysticerci.
- Toxicological tests show that this product is less toxic and safe. The oral LD50 of mice is more than 800mg / kg, and the maximum oral tolerance of dogs is more than 400mg / kg. The drug has no effect on the reproductive function of male mice, and it has no teratogenic effect on female mice. Fetal absorption and bones can occur in female rats and female rabbits at higher doses (30mg / kg / day). Deformity, etc.
Application of albendazole
- This product is a new high-efficiency, broad-spectrum insecticide. It is a kind of benzimidazole that has a broader insect-repelling spectrum and the strongest insecticidal effect. It is highly active against nematodes, schistosomiasis, and roundworms, and has a significant inhibitory effect on egg development. Albendazole treats parasites, but is not effective against insects.
- It also has obvious repellent effect on various nematodes, schistosomiasis, tapeworms and cysticercaria parasitic on animals. Suitable for
- Albendazole molecular formula (2 photos)
Albendazole dosage
- Take orally to drive hookworms, roundworms, roundworms, whipworms, 0.4g. Ascaris lumbricoides and Ascaris lumbricoides infection in children over 2 years of age, 0.2 g serving.
- Treatment of cysticercosis: 15-20mg / kg daily, divided into two doses. 10 days is a course of treatment. After 15 to 20 days of withdrawal, the second course of treatment can be performed. Usually 2 to 3 courses. Repeat treatment if necessary.
- Other parasites, such as trichomes, are administered 400 mg daily for 6 days. Repeat administration if necessary. Half the dosage for children under 12 years old. Do not need to fast or clear the intestines before taking the medicine, but can be taken with food after chewing, swallowing or grinding.
Albendazole precautions
- (1) A few cases have mild headache, dizziness, nausea, vomiting, diarrhea, dry mouth, fatigue and other adverse reactions, which can disappear without treatment.
- (2) Disabled for children and pregnant women under 2 years old.
- (3) It should not be used in patients with acute diseases, proteinuria, purulent or diffuse dermatitis, epilepsy, etc., and breast-feeding women. Use with caution in patients with severe liver, kidney, and heart dysfunction and active ulcer disease.
- (4) A small number of patients may experience deworming effects after taking 3-10 days.
- (5) During the treatment of cysticercosis, some patients will experience dizziness, headache, fever, urticaria and other reactions to varying degrees. The degree of reaction is related to the number of cysticercosis, parasitic sites and body reactions. Patients with severe infections must be hospitalized for cerebrospinal fluid and fundus examinations, and closely monitored. If necessary, dexamethasone, 20% mannitol can be given as appropriate. No treatment is required for dermatocystis.
Albendazole pharmacokinetics
- Albendazole is insoluble in water, so it is absorbed slowly in the intestine. The original drug is converted into prothiobenzimidazole-sulfoxide and prothiobenzimidazole-sulfone in the liver, the former being an insecticidal component. This product is distributed in the body in the order of liver, kidney, muscle, can penetrate the blood-brain barrier, and there is a certain concentration in brain tissue. Peak blood concentration reached 2.5 to 3 hours after oral administration. The concentration of the original drug and the sulfone derivative in the blood is extremely low and cannot be measured. The concentration of prothiobenzimidazole-sulfoxide varies greatly, ranging from 0.04 g / ml to 0.55 g / ml, with an average of 0.16 g / ml. The half-life (t1 / 2) in blood is 8.5 to 10.5 hours. 87% of this product and its metabolites are excreted from urine and 13% are excreted from feces within 24 hours, and have no accumulation effect in the body.
Albendazole adverse reactions
- 1. Can cause encephalitis syndrome, mostly delayed reactions.
- 2. A few cases have symptoms such as dry mouth, fatigue, sleepiness, dizziness, headache, and nausea and epigastric discomfort. However, all of them are minor and can be relieved without treatment.
- 3. A small number of patients may have skin damage such as drug rash and exfoliative dermatitis; white blood cells (especially granulocytes) and thrombocytopenia may occur.
- 4. In the treatment of porcine cysticercosis, the dosage is large and the treatment period is long. The reaction usually occurs 2 to 7 days after taking the drug. There are headache, fever, rash, muscle soreness, seizures, etc. These symptoms are opposite to the death of cysticercosis. Protein and other factors are related, corresponding measures must be taken (application of adrenal cortex hormones, lowering of intracranial pressure, anti-epileptic treatment). [3]
Albendazole contraindications
- 1. Allergies, those with a history of allergies and family allergies to this product are prohibited.
- 2. Pregnant women and lactating women are prohibited.
- Children under 3.2 are disabled.
- 4. Liver and kidney dysfunction are disabled. [3]
Albendazole administration instructions
- 1. The various parasites in the indications are different in the human body. The concentration of the drug in the intestine and tissues after oral administration is very different. In addition, the thickness of the cortex of various worms is different, so the clinical species are different. The doses used vary widely.
- 2. Combined with thiapyrimidine, it can eliminate adverse reactions caused by the movement of worms (such as vomiting, abdominal pain, biliary maggots, and vomiting maggots, etc.), and can enhance the deworming effect. [3]
Albendazole preparations and specifications
- 1. Albendazole tablets: 100mg; 200mg.
- 2. Albendazole capsule: 200mg.
- 3. Compound albendazole tablets: Each tablet contains 67mg of albendazole and 250mg of thiapyrimidine. [3]