What Is Griseofulvin?
Griseofulvin is a white or off-white fine powder; odorless and slightly bitter. This product is easily soluble in dimethylformamide, slightly soluble in anhydrous ethanol, and very slightly soluble in water. The melting point is 218-224 ° C. Griseofulvin is mainly used clinically for tinea capitis, severe tinea corporis, shingles, and onychomycosis of hands and feet.
- Chinese name
- Griseofulvin
- English name
- Griseofulvin
- nickname
- Cineomycin
- Chemical formula
- C17H19ClO6
- Molecular weight
- 354.7822
- CAS Registry Number
- 126-07-8
- EINECS registration number
- 204-767-4
- Griseofulvin is a white or off-white fine powder; odorless and slightly bitter. This product is easily soluble in dimethylformamide, slightly soluble in anhydrous ethanol, and very slightly soluble in water. The melting point is 218-224 ° C. Griseofulvin is mainly used clinically for tinea capitis, severe tinea corporis, shingles, and onychomycosis of hands and feet.
Griseofulvin drug name
- Chinese name:
- English alias: grisovin; 7-chloro-2 ', 4,6-trimethoxy-6'-methyl-3H, 4'H-spiro [1-benzofuran-2,1'-cyclohex [2] ene] -3,4 '-dione; (2S, 6'R) -7-chloro-2', (the same as the previous boldface); (2R, 6'S) -7-chloro-2 ', (the same as the previous boldface)
- Candida
- Molecular weight: 354.7822
- Density: 1.35g / cm 3
- Melting point: 217 224 ° C
- Boiling point: 527.9 ° C at 760 mmHg
- Flash point: 205.9 ° C
- Vapor pressure: 3.11E-11mmHg at 25 ° C
- Uses: It has an inhibitory effect on a variety of dermatophytes and is effective against vigorously growing fungi.
Griseofulvin pharmacological action
- Can inhibit fungal mitosis, break the spindle structure of mitosis, and terminate cell division in the middle stage. This product is deposited in the keratin precursor cells of the skin and hair, which can promote the keratin to resist the invasion of fungi; when the infected keratin falls off, it is replaced by healthy tissue. Effective against skin fungal infections caused by Epidermophyton, Microsporum and Trichophyton, and against other fungi
- Cortisol
Griseofulvin determination method
- Method name: Griseofulvin API-Griseofulvin-High Performance Liquid Chromatography
- Scope of application: This method uses high performance liquid chromatography to determine the content of griseofulvin in griseofulvin raw materials.
- This method is applicable to griseofulvin.
- Principle of the method: The test sample was dissolved and diluted with mobile phase, and then entered into a high performance liquid chromatography for chromatographic separation. The ultraviolet absorption detector was used to detect the peak area of griseofulvin at a wavelength of 254 nm and calculate its content.
- Reagent: 1. Acetonitrile
- Methanol
- 3. 0.05mol / L potassium dihydrogen phosphate solution
- 4. Phosphoric acid
- Equipment: 1. Instrument
- 1.1 HPLC
- 1.2 Column
- Octadecylsilane-bonded silica gel is used as a filler, and the theoretical plate number should not be lower than 800 based on the griseofulvin peak.
- 1.3 UV absorption detector
- Chromatographic conditions
- 2.1 Mobile phase: 0.05mol / L potassium dihydrogen phosphate solution acetonitrile methanol = 57 38 5, adjust the pH value with phosphoric acid 3.7 ± 0.2
- 2.2 Detection wavelength: 254nm
- 2.3 Column temperature: room temperature
- Sample preparation: 1. Preparation of reference solution
- Precisely weigh about 50mg of griseofulvin reference substance, place it in a 50mL volumetric flask, add the mobile phase to dissolve and dilute to the mark, take 5mL precisely, place it in a 50mL volumetric flask, add the mobile phase to dilute to the mark, and shake to obtain Control solution.
- 2. Preparation of test solution
- Take 10 test samples, accurately weigh, grind carefully, accurately weigh an appropriate amount (approximately 100mg of flavomycin), put it in a 100mL volumetric flask, add an appropriate amount of mobile phase, sonicate for 30 minutes, and let it cool to room temperature. Add mobile phase to scale, shake well, filter through 0.45 & micro; m microporous filter, accurately measure 5mL of the filtrate, place it in a 50mL volumetric flask, add mobile phase to scale, shake and mix, it is the test product Solution.
- 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.
- Operation steps: Precisely draw 10 mL of each of the reference solution and the test solution, and inject them into a high-performance liquid chromatograph. Use an ultraviolet absorption detector to measure the peak area of griseofulvin (C17H17ClO6) at a wavelength of 254 nm and calculate its content.
- References: Pharmacopoeia of the People's Republic of China, compiled by the National Pharmacopoeia Committee, Chemical Industry Press, 2005 edition, Part Two, p.192.
Griseofulvin kinetics
- Absorption from the digestive tract is very irregular, and the difference is large. Microparticles of flavomycin are absorbed by 25 to 75% after oral administration, and ultrafine particles of flavomycin are almost completely absorbed. After absorption, it deposits in the keratin of the skin, hair and nails, and can be detected in the stratum corneum of the skin after several hours of oral administration. Only a small part is distributed in body fluids and tissues. A single dose of 500 mg orally, the blood concentration reached a peak within 24 hours, and T1 / 2 (half-life) was about 24 hours. It is mainly metabolized in the liver as 6-norgriflavin and excreted with urine. Less than 1% at a time, excreted from the urine in the original form, the non-absorbed part
- Yeast
Griseofulvin indication
- Suitable for skin fungal infections caused by Epidermophyton, Microsporum and Trichophyton. It is mainly used clinically for tinea capitis, severe tinea corporis, shingle ringworm, onychomycosis of hands and feet, etc., and it has obvious curative effect on tinea capitis. Some cases may recur, but retreatment still works. For nail ringworm, it usually takes several months to take effect, so it is advisable to use other medications. It also has a certain therapeutic effect on shingles [2] [1] .
Griseofulvin Usage and Dosage
- Oral, 0.2-0.25g once, 0.8-1g per day. Generally, a large amount can be used at first, the amount is 1g per day, and it is reduced to 250-500mg after marked effect. After meals, the treatment course is 20-30 days. At the same time, it is combined with a topical fungicide. For children, the dosage is 15-20mg / kg per day, divided into 3 to 4 times. Taken at meals or after meals can reduce gastrointestinal irritation; Give a high-fat diet to promote absorption;
- Urticaria
Griseofulvin adverse reactions
- 1. Rarely may be insanity, rash (urticaria, pruritus), mouth or tongue pain or irritation, and thrush [2] .
- 2. Numbness, tingling, pain, or weak hands and feet (peripheral neuritis) can be seen when taking long-term or large doses.
- 3. Others may include headache, diarrhea, dizziness, nausea, vomiting, stomach pain, insomnia, and abnormal fatigue. Can cause gastrointestinal reactions: nausea, vomiting, loss of appetite, bloating, diarrhea, headache, lethargy, rash, fever, joint pain
- Hepatocyte
- nervous system
- You can see sleepiness, dizziness, fatigue, insanity, depression, but you can also see irritability and insomnia. Headaches account for about 50% and are sometimes severe. In some patients, ataxia and difficulty in walking can be seen during insanity. Peripheral neuritis, taste disorders, tinnitus, visual impairment, feminization of male breasts, etc. may occur. Mental symptoms can be exacerbated by taking alcoholic beverages.
- Digestive system
- Can produce black tongue fur, tongue pain, angular cheilitis and taste disorders. Common mild nausea and diarrhea, loss of appetite, and heavy feeling in the upper abdomen. Vomiting, abdominal pain and severe diarrhea are rare. There have been reports of "hepatitis", "reversible intrahepatic cholestasis" and BSP retention, the cause of which is unknown. This product interferes with the metabolism of porphyrins. In the human body, the concentration of endogenous porphyrins in red blood cells can be increased, and the production and excretion of porphyrins will increase. Animal experiments indicate that delta-aminolaevulinicacid synthesis is increased, causing porphyrin to accumulate in liver cells. Hematopexin was found to increase in experimental animals, and hepatomas may develop.
- Urinary system
- There have been reports of abnormal proteinuria and non-specific urine sediment, and no renal damage has been seen.
- Lupus erythematosus
- Visible leukocytopenia, neutropenia, eosinophilia, and increased monocytes. However, there is no further confirmation that this product can cause severe hematological lesions. Some people think that this product can stimulate the appearance of whole body lupus erythematosus.
- Endocrinology, metabolism
- There are reports of estrogen-like effects in children that affect the reproductive system and the breast. [Skin] Itchy skin, rash, urticaria, xanthomas, measles-like rash, scarlet fever-like rash, and sensitive to sunlight, while erythema polymorpha, herpes, fixed drug rash, cutaneous vasculitis, and even rubbing rosary Mycosis (Candidaintertrigo) is rare [2] .
Griseofulvin contraindications
- 1. Patients who are allergic to penicillin and its derivatives can also be allergic to this product.
- 2. Animal studies have shown toxicity to embryos. Can cause teratogenic, pregnant women are prohibited.
- Erythromycin
- liver failure;
- Lupus erythematosus;
- Porphyria. Intermittent porphyria is absolutely contraindicated; other forms of porphyria should also be avoided. Hepatic insufficiency should be used with caution. Pregnant women are contraindicated [2] .
Griseofulvin interactions
- 1. Taking this product together with ethanol can enhance the effect, but tachycardia and flushing can occur.
- 2. Sharing with barbiturates or coumarin anticoagulants can reduce the efficacy, which requires regular prothrombin time. Avoid drinking alcohol during the application of this product, because this product can strengthen the effect of ethanol. With enzymatic effect, it can weaken the anticoagulant effect of warfarin. In combination with barbiturates, the effect of this product is weakened.
Griseofulvin drug tablets
Griseofulvin dose
- Griseofulvin tablets 0.1g 0.25g taken orally, 0.5 1g a day, divided into 2 times or taken. Marked effect
- Phenylethanol
Griseofulvin pharmacological action
- This product mainly has good antibacterial effect on Trichophyton, Trichophyton, Epidermophyton and other superficial fungi. It has no antibacterial effect on Candida, Cryptococcus, Histoplasma, Sporothria, Sporophyte, Coccus. The drug system inhibits the growth of fungal nucleic acid by interfering with its synthesis. This product is white or off-white film.
Griseofulvin kinetics
- The oral absorption of this product varies depending on the preparation. The particulate type of the drug can be absorbed by 25% to 70%, and the ultrafine type is almost completely absorbed after oral administration. Eating fat can significantly increase the extent of absorption. The serum protein binding rate of this product is about 80%. This product can be deposited on the cuticle of skin, hair and nails after absorption, and combine with its keratin to prevent the continued invasion of sensitive dermatophytes, etc. Pathogenic fungi existing in the superficial stratum corneum fall off with the skin or hair When leaving the body, only a small amount is distributed to other body fluids and tissues. This product can also enter the fetal circulation and be secreted from milk. This product is metabolized and inactivated in the liver. The main metabolite is 6-methylgriseofulvin and its glucose.
- Nuclei
Griseofulvin indication
- This product is suitable for the treatment of various ringworm diseases, including tinea capitis, ringworm, tinea corporis, jock itch, tinea pedis, and onychomycosis. The above mentioned ringworm diseases include trichophyton rubrum, ringworm trichophyton, ringworm trichophyton, etc., and micro-sporidium aduanum, microsporium canis, gypsum-like microsporum, and floccus epidermophyton. Caused by. This product should not be used for mild, localized and superficial fungal infections and topical antifungal drugs. Griseofulvin is not effective against infections such as Candida, Histoplasma, Actinomyces, Sporothrix, Bacillus, Coccidia, Nocardia and Cryptococcus .
Griseofulvin Usage and Dosage
- The following are the doses for the particulate type. Adults: onychomycosis and athlete's foot, 500 mg once every 12 hours; tinea capitis, tinea corporis, or jock itch, 250 mg once every 12 hours, or 500 mg once daily. Pediatrics: those over 2 years of age who weigh 14 to 23 kg, 62.5 to 125 mg once, once every 12 hours, or 125 to 250 mg once daily. Children with a weight of more than 23 kg, 125 to 250 mg once, once every 12 hours, or 250 to 500 mg once daily.
Griseofulvin adverse reactions
- 1. Nervous system headaches are more common, about 10% of patients may have headaches, which are heavier at first
- Plasma protein
- 2. A small number of patients with digestive system may experience epigastric discomfort, nausea or diarrhea, which is generally mild and can be tolerated by patients.
- 3, allergic reactions can occur in about 3% of patients with rash, occasionally angioedema, persistent urticaria, exfoliative dermatitis, a few patients can develop photosensitivity dermatitis.
- 4. This product can cause reduction of peripheral leukocytes, and can cause liver toxicity and proteinuria.
Griseofulvin contraindications
- Porphyria, liver failure, pregnant women and those who are allergic to this product are contraindicated [2] .
Griseofulvin precautions
- 1. Cross-sensitivity Because griseofulvin is obtained from penicillium, it is speculated that the drug may be cross-allergic with penicillins or penicillamine, but this has not been confirmed clinically, but patients with penicillin allergies still need to use this product Be careful and observe closely.
- 2. Griseofulvin has tumorigenic effects in animal experiments.
- 3. This product can cause hepatotoxicity. Those with original liver disease or liver function impairment need to weigh the advantages and disadvantages before deciding whether to take the drug.
- 4. This product can induce porphyria and lupus erythematosus. Patients with lupus erythematosus must weigh the advantages and disadvantages before using the drug if they are instructed.
- 5. During the treatment, the peripheral blood, liver function, blood urea nitrogen, creatinine and urine routine should be tested regularly.
- 6. This product can be taken with or after meals. It is best to eat high-fat meals because it can reduce
- Central nervous system
- 7. To prevent recurrence, treatment should be continued until clinical symptoms disappear and laboratory tests confirm that the pathogen has been completely eradicated. The general course of treatment is: tinea capitis 8-10 weeks; ringworm 2-4 weeks; tinea pedis 4-8 weeks; nail ringworm at least 4 months; toenail ringworm at least 6 months;
- 8. Appropriate topical medication is usually required at the same time, which is especially important for athlete's foot.
- 9. Male patients should take contraception during treatment and at least 6 months after the end of treatment. Information on the use of this product is lacking in children under 2 years of age. Animal experiments have confirmed that this product has teratogenic effects, so pregnant women are contraindicated. Women of childbearing age are treated with contraception during treatment and continue until 1 month after the end of treatment. There is no research data on the application of this product in the elderly and its relationship with age [2] .
Griseofulvin overdose
- Drug overdose is mainly symptomatic and supportive therapy, such as gastric lavage, use of emetics and rehydration [2] .
Griseofulvin interactions
- 1. This product and ethanol can cause tachycardia, sweating, flushing of the skin, etc., so the two are not suitable.
- Fungus
- 2. When combined with anticoagulants such as warfarin and coumarins, this product may enhance liver metabolism and weaken the effect of anticoagulants, so it is necessary to monitor the prothrombin time to adjust the dose.
- 3. The antifungal effect of this product can be weakened when combined with phenidone and phenobarbital. It may reduce the absorption of the drug with barbiturates and inactivate this product due to the effects on liver enzymes. Increasing the speed and reducing the concentration of blood drugs, such drugs should be avoided in combination with this product.
- 4. The combination of estrogen contraceptives and this product can reduce the effect of oral contraceptives.
- Penicillium
Griseofulvin preparation
- Calculated as C17H17ClO6 (1) 0.1g (2) 0.25g [2]
Griseofulvin manufacturers
- Guangdong Pidi Pharmaceutical Co., Ltd., Guangdong Jiangmen Huanyu Pharmaceutical Co., Ltd., Nikme Pharmaceutical Co., Ltd., Guangdong Bangmin Pharmaceutical Factory Co., Ltd., Guangdong Nanguo Pharmaceutical Co., Ltd., Hubei Zhongtian Aibai Medicine Co., Ltd. Group companies Shenyang Keda Co., Ltd., Lanzhou Pharmaceutical Factory, Zhangfeng Pharmaceutical Factory in Longchuan County, Yunnan Province, Xi'an Lijun Pharmaceutical Co., Ltd., Chongqing Kerui Pharmaceutical Co., Ltd., Liuzhou Pharmaceutical Factory, Chengdu Pharmaceutical Co., Ltd., Guangzhou Guanghua Pharmaceutical Co., Ltd., Shenzhen Changbaishan Pharmaceutical Factory Industry Co., Ltd., Wuhan Pharmaceutical Group Co., Ltd., Henan Zhongfu Pharmaceutical Co., Ltd., Zhejiang Yuyao Pharmaceutical Factory, Wuhan Antibacterial
- bacterial
Griseofulvin drug development
- The oral antifungal drug griseofulvin only became available in the late 1950s. Later, imidazoles such as ketoconazole, and a new generation of triazole antifungals such as itraconazole, fluconazole, and propylene were discovered. Netil
- leukocyte
- Griseofulvin is a chlorine-containing antibiotic. It is a white cream-colored powder or crystal. It is soluble in methanol, ethanol, ether, chloroform, and acetone. It is difficult to dissolve in water. Can inhibit various dermatophytes in test tubes, including Epidermophyton, Microsporum and Trichophyton. It has no antibacterial effect on Candida and other fungi that cause deep infections.
- This medicine is not easy to penetrate the cuticle of the epidermis, so it is not effective for external use. As this drug is orally hepatotoxic, it should be regularly checked for liver function, blood, and porphyrin excretion in urine. This medicine can cure more than 90% of tinea capitis caused by various fungi. In some cases of recurrent tinea capitis, it is still effective. It usually takes 2 to 3 weeks as a course of treatment. Fungal infections in other areas are rarely used clinically.
Severe illness caused by griseofulvin
- Medical record summary
- Patient, female, 44 years old. She was mainly seen in the emergency department of our hospital due to bullous skin lesions of the face and upper limbs. She was transferred to our department and asked for a detailed medical history. Oral flavomycin for the treatment of onychomycosis (Xi'an Lijun Pharmaceutical Co., Ltd.) ) 5 tablets / time, skin lesions appear the next day after 3 times a day. The patient denied any other and drug allergies. Physical examination: Generally good. Dermatological conditions: The entire face, arms to arms and back can be seen in different sizes, large, about the size of eggs, loose blisters, some of the blisters have been damaged, the blisters have flowed out, the back is bright red, and flakes have been formed by touching the skin with your hands. No erosion or exudation was seen in both eyes and oral mucosa. Blood test routine: 11.4% monocytes, normal white blood cells, and no eosinophils detected. Urine routine: urinary occult blood (+++). According to the patient's main complaint, the cause was clear, and the diagnosis was severe drug eruption (photosensitive type).
- Administration of hormones, antihistamines, and antibiotics to prevent secondary infections and local symptomatic treatment. Due to the general condition of patients, oral prednisone and calcium preparations, intravenous drip antibiotics, VitC, VitB6, 10% glucose solution 1000ml, once a day for 1 week, the skin lesions were extracted under aseptic operation, Topical calamine lotion and eutrol ointment, the patient was revisited 3 days later (due to an incident at home, requiring outpatient treatment), the skin lesions had healed 50%, and the urine routine was reviewed after 1 week: occult blood (+). After continued oral antibiotics for 20 days, the urine routine returned to normal, and the skin lesions basically recovered after 3 weeks, with occasional mild pigmentation.
- Expert discussion
- The author has not encountered this serious drug eruption in the skin profession for many years. Griseofulvin has a positive effect on the prevention and treatment of skin fungal diseases, especially phototinea. It is one of the effective drugs for the prevention and treatment of skin fungal diseases. It is deposited in the stratum corneum of the skin after oral administration and is combined with skin hair follicles and keratin. In order to prevent the fungus from continuing to invade, the pathogen will leave the human body with the natural shedding of skin and hair. Toxic and adverse reactions Animal experiments have found toxic hepatitis and kidney damage, increased protoporphyrin in erythrocytes in the urine, clinical gastrointestinal reactions, headache, and photosensitive dermatitis. In this case, the medication was clear, the skin lesions were mainly light-prone sites, and occult blood appeared routinely. Therefore, the author believes that it is a typical allergic photosensitivity dermatitis type. I have repeatedly instructed the patients to absolutely prohibit the use of griseofulvin and drugs with similar chemical structure. In order to prevent the occurrence of cross infection, patients or family members with a history of allergic diseases should pay special attention.