Target: Spindle microtubules (MTs)
Microtubule-associated proteins (MAPs) [1]
Ferrochelatase [1]
Cytochrome P-450 [1]

Griseofulvin is active against dermatophytes of different species in the genera Microsporum, Trichophyton and Epidermophyton. Other fungi such as Scopulariopsis brevicaulis and Hendersomula toruloidea are insensitive. Griseofulvin has little or no effect against yeasts and bacteria. The minimum inhibitory concentration of Griseofulvin tested in vitro against various dermatophytes ranges between 0.14 and 0.6 μg/mL. Main effect of Griseofulvin on cell mitosis is disorganization of the spindle microtubules. Griseofulvin is also able to induce structural chromosomal aberrations in mammalian cells. Griseofulvin inhibits the viability of human colon adenocarcinoma cells COLO 205 and HT 29, hepatoma cells Hep G2 and Hep 3B, leukemia cells HL 60, and normal keratinocytes (#76 KhGH) with IC50s of ~1 and ~5 μM, 5 and 5 μM, 1 μM, and 50 μM, respectively after a 30 hr incubation,. Griseofulvin (20 μM) induces a marked presence of abnormal mitotic spindle formation with mono-, bi-, and tripolar spindles of varying lengths in HT 29 cells, and causes G2/M cell cycle arrest at 24h through elevation of cyclin B1/cdc2 kinase activity and down-regulation of myt-1 protein expression. Griseofulvin is able to induce apoptosis of HT 29 cells via caspase3 activation, Bcl-2 hyperphosphorylation and inhibition of the normal function of Bcl-2 associated with Bax.

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Cell Assay: The cells (5× 103/mL) are incubated in triplicate in a 96-well plate in the presence or absence of indicated concentration of Griseofulvin in a final volume of 0.2 mL for different time intervals at 37 ℃. Thereafter, 20 μL MTT solution (5 mg/mL in PBS) is added to each well. After a 2-hour incubation at 37 ℃, 0.1 mL lysis buffer (20% SDS, 50% dimethylformamide) is added, incubation is continued overnight at 37 ℃, and then the optical density at 570 nm is measured by plate reader.

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In Vitro: Griseofulvin is active against dermatophytes of genera Microsporum, Trichophyton and Epidermophyton with minimum inhibitory concentrations ranging between 0.14 and 0.6 μg/ml. Abnormal hyphal development is observed at doses of 0.1-0.2 μg/ml. [1]
In the human heteroploid EUE cell line, a 3-day treatment with Griseofulvin at concentrations from 0.39 to 50 μg/ml reduced plating efficiency, with drastic reduction at 12.5 μg/ml (PE 0.052) and 25 μg/ml (PE 0.039). Colony size was also strongly inhibited starting from 12.5 μg/ml (93.86% reduction). [1]
Griseofulvin causes mitotic arrest at late metaphase/early anaphase in various cell systems including Vicia faba, Allium root tips, HeLa, CHO and PTK1 cells. Effects include C-metaphases, lobulated metaphases, ball metaphases, lagging chromosomes, interchromosomal bridges, and multipolar spindles. [1]
In PTK1 cells, Griseofulvin at 2.5×10⁻⁶ to 2.5×10⁻⁴ M causes progressive loss of birefringence and shortening of pole-to-pole distance. [1]
In common wheat root tip cells, 6h treatment with Griseofulvin at 1.5×10⁻⁵ M induced ~50% partially affected metaphases; at 3×10⁻⁵ M, ~90%; at ≥4.5×10⁻⁵ M, all metaphases were irregular. Multipolar anaphases increased in parallel. [1]
Griseofulvin inhibits the regeneration of cilia in Stentor. [1]
Griseofulvin at 10⁻⁴ M inhibits in vitro microtubule polymerization by about 60% as measured by viscometry. [1]
Griseofulvin increases the frequency of cell transformation induced by polyoma virus in mouse 3T3 cells, with a >38-fold increase at 1.95 ng/ml. At concentrations ≥0.5 μg/ml, transformation frequency is reduced, and at 25 μg/ml it is totally inhibited. [1]
Griseofulvin alone does not induce cell transformation in the Syrian hamster embryo transformation assay (0.25-1.0 μg/ml, no transformed colonies out of >5000 scored). [1]
Griseofulvin treatment (40 μg/ml) of BHK 21 cells did not induce colony growth in soft agar, indicating no evidence of cell transformation. [1]
In CHO-K1 cells, no cells were killed at Griseofulvin concentrations from 10⁻⁶ to 10⁻⁴ M, and only 20% failed to survive at 10⁻³ M. [1]

Griseofulvin displays potent anti-infection activity in vivo. The minimum effective dose of Griseofulvin given daily per os is 250 mg/kg (6 days) in mice with a cutaneous infection of Trichophyton quinckeanum and 25 mg/kg (12 days) in guinea pigs with a cutaneous infection of Trichophyton mentagrophytes. Griseofulvin (50 mg/kg) is able to suppress COLO 205 tumor xenografts growth. Treatment with Griseofulvin and nocodazole (5 mg/kg) together significantly enhances the efficacy of nocodazole, leading to cessation of tumor growth.
In Vivo: In mice with cutaneous infection of Trichophyton quinckeanum, the minimum effective daily oral dose of Griseofulvin was 250 mg/kg (×6 days). In guinea pigs with Trichophyton mentagrophytes infection, it was 25 mg/kg (×12 days). [1]
In mice fed a diet containing 2.5% Griseofulvin, Mallory bodies appeared in a high proportion of hepatocytes after 120-200 days of treatment. [1]
In mice continuously treated with Griseofulvin, derangement of porphyrin metabolism is followed by liver hypertrophy, extensive liver damage, development of biliary cirrhosis, and ultimately multiple hepatomas. [1]
Oral administration of Griseofulvin leads to the promotion of initiated skin tumors (methylcholanthrene-induced). [1]
In pregnant rats exposed during organogenesis, Griseofulvin at oral doses of 1250 and 1500 mg/kg/day affects embryo development, reduces survival, and causes malformations including tail anomalies, lack of eyes, anal atresia and exencephaly. [1]
Micronized Griseofulvin dissolved in PEG 300 at doses of 50, 250, 500 mg/kg administered on days 6-15 of pregnancy in rats caused dose-dependent reduction of pup birth weight, decreased number of live fetuses, and increased resorptions, skeletal variations and malformations. [1]
A depression of the cellular immune response has been observed in mice treated with 1% Griseofulvin in the diet for 4-6 weeks. [1]
Griseofulvin has been shown to inhibit polymorphonuclear chemotaxis in Boyden chambers. [1]

Enzyme Assay: Griseofulvin’s effect on porphyrin metabolism was studied by measuring protoporphyrin accumulation in mouse liver. Protoporphyrin increased from about 1.5 nmoles/g to an average of 260 nmoles/g wet weight after 3 days of treatment, and could reach above 8000 nmoles/g after 2-3 months of feeding. The accumulation was attributed to decreased ability to convert protoporphyrins into heme due to diminution of hepatic ferrochelatase activity. A strong inhibitory activity towards ferrochelatase was demonstrated for a modified porphyrin produced by Griseofulvin treatment. [1]
The effect of Griseofulvin on hepatic microsomal enzymes was studied in mice treated with 2.5% GF in the diet for 12 days. Results showed a 50% reduction in cytochrome P-450 and a 2-fold increase in cytochrome b₅. Lipid peroxidation may be involved as suggested by membrane damage and brown pigment deposition. [1]
In another study, short-term Griseofulvin treatment (2.5% w/w for 4 days) in mice increased 5-aminolevulinate synthase activity to about 6 times control values and decreased ferrochelatase activity to 13.5% of initial values. [1]
The ability of Griseofulvin to inhibit microtubule polymerization in vitro was quantitatively determined by viscometry, giving a value of about 60% inhibition of polymerization at 10⁻⁴ M. Gel electrophoresis studies of MT material reassembled from purified tubulin in the presence of GF indicated that MTs are depleted in high molecular weight components of MAPs, suggesting GF might influence MAPs interaction with tubulin. [1]

Cell Assay: For cell survival and growth assays, human heteroploid EUE cells were seeded at 500 cells/well in 24-well multiplates and treated with Griseofulvin at concentrations ranging from 0.39 to 50 μg/ml for 3 days. After treatment, cells were grown for 6 days, and plating efficiencies and average number of cells per colony were determined. Plating efficiency was calculated as (average number of colonies/well) / (number of cells seeded) × 100%. Results showed drastic reduction in PE at 12.5 μg/ml (0.052) and 25 μg/ml (0.039), with colony size reduction of 93.86% and 94.42% respectively. [1]
To study mitotic effects, various cell systems including Vicia faba, Allium root tips, HeLa, CHO, PTK1, and human lymphocytes were treated with Griseofulvin at different concentrations. Cells were examined by light microscopy, polarization microscopy, immunofluorescence with tubulin antibodies, and electron microscopy. Mitotic arrest at late metaphase/early anaphase was observed, with C-metaphases, lobulated metaphases, ball metaphases, lagging chromosomes, bridges, and multipolar poles. In PTK1 cells treated with 2.5×10⁻⁶ to 2.5×10⁻⁴ M GF, progressive loss of birefringence and shortening of pole-to-pole distance were observed. [1]
For multinuclearity quantification, cells were treated with Griseofulvin at various doses and incubation times. The frequency of multinucleated cells was measured. In human PHA-stimulated lymphocytes, frequency was 30% after 3 days of treatment with 40 μg/ml GF. In human heteroploid EUE cells, it reached 95% at the same concentration. Multinucleated cells were shown to be viable for prolonged periods and resumed division when returned to drug-free medium. [1]
To study cell transformation, mouse 3T3 cells in the resting phase were treated with Griseofulvin at concentrations of 0.97-500 ng/ml for 7 days after infection with polyoma virus. Cultures were grown for an additional 25 days in medium without the drug and scored for transformed cell foci. The most effective concentration was 1.95 ng/ml, giving >38-fold increase. In Syrian hamster embryo transformation assay, cells were treated with 0.25-1.0 μg/ml GF for 7 days, and no transformed colonies were detected out of >5000 scored colonies. [1]
For chromosome segregation studies, human PHA-stimulated lymphocytes and EUE cells were treated with Griseofulvin at 20-40 μg/ml for 3 days, then allowed to recover in normal medium. Chromosome number distributions were analyzed at various recovery times. Maximum scattering of chromosome numbers was observed after 3 days recovery in EUE cells (range 30-150) and immediately after treatment in lymphocytes. [1]
To assess aneuploidy using chromosome-specific DNA probes, human lymphoblastoid cells or PHA-stimulated lymphocytes were treated with Griseofulvin at 5, 10, and 20 μg/ml. In situ hybridization was performed on interphase nuclei using probes specific for chromosome 9 (QP23) and Y chromosome (Y97). A marked increase in aneuploid nuclei frequency was observed, with Y97 probe showing 0.15% (control), 0.64% (5 μg/ml), and 1.15% (10 μg/ml); QP23 probe showing 0.30% (control), 0.90% (5 μg/ml), 3.00% (10 μg/ml), and 2.00% (20 μg/ml). [1]

Dissolved in DMSO; 50 mg/kg; i.p. injection Human colon adenocarcinoma xenografts COLO 205

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Animal Protocol: For in vivo efficacy studies, mice with cutaneous infection of Trichophyton quinckeanum were given Griseofulvin daily per os at 250 mg/kg for 6 days. Guinea pigs with cutaneous infection of Trichophyton mentagrophytes were given 25 mg/kg daily per os for 12 days. [1]
For carcinogenicity studies, AP stock mice were fed a diet containing 0.5% or 1% Griseofulvin for 400-435 days. Hepatomas were observed in 5/20 and 10/13 mice, respectively. In another study, mice were treated with 1% GF in the diet for 12-16 months, with sex differences in hepatoma incidence. Mice were also given subcutaneous or intramuscular injections of 3 mg/animal GF within the 21st day of age, resulting in highly significant differences in hepatoma incidence. Rats were treated with 0.2%, 1.0%, or 2.0% GF in the diet continuously or during alternate 5-week periods for life, resulting in dose-related increase in thyroid tumors. Hamsters were treated with 0.1-3% GF in the diet with negative results. [1]
For teratogenicity studies, pregnant rats were exposed during organogenesis to oral doses of Griseofulvin at 1250 and 1500 mg/kg/day. In another study, micronized GF dissolved in PEG 300 was administered at doses of 50, 250, 500 mg/kg on days 6-15 of pregnancy. Fetal death rate was highest when GF at 50 or 500 mg/kg was administered from days 7 to 10 of pregnancy, while highest fetal malformations were found from days 11 to 14. [1]
For Mallory body induction, Swiss albino mice were fed a standard diet containing 2.5% Griseofulvin, and MBs appeared in a high proportion of hepatocytes after 120-200 days of treatment. [1]
For porphyria studies, mice were fed a diet containing 1% or 2.5% Griseofulvin for various periods. Protoporphyrin accumulation in liver was measured after 3 days, 2-3 months, and longer periods. [1]
For acute toxicity, rats received intravenous injection of Griseofulvin at about 400 mg/kg (LD50) or intraperitoneal doses up to 2 g/kg. Mice and rats tolerated single oral doses of 50 g/kg and 10 g/kg respectively. [1]

Absorption, Distribution and Excretion
After oral administration, gastrointestinal absorption is low, ranging from only 25% to 70% of the oral dose. Concomitant administration with a fatty meal or after a meal significantly improves absorption. In rats, after oral administration of 100 mg/kg body weight (36) CL-griseofulvin, 10% of the active substance was detected in urine 24 hours later, and 4% was detected within 24–48 hours. …Another study showed that after oral administration of a similar dose in rats, only 0.14% of the active substance was detected in urine within 24 hours, and 16% in feces. After intravenous injection, griseofulvin was evenly distributed in various tissues, but higher concentrations were observed in the skin and lungs. Microparticles—absorption is variable, ranging from 25% to 70% of the oral dose. Ultramicroparticles—almost completely absorbed. Concomitant administration with a fatty meal or after a meal significantly improves absorption. Griseofulvin is deposited in varying concentrations in the stratum corneum of the skin, hair, and nails. It is detectable in the stratum corneum of the skin within hours of administration. Only a very small fraction of the oral dose is distributed in body fluids and tissues. Excretion: Excreted by the kidneys. Less than 1% of the dose is excreted unchanged in the urine. Approximately 36% of griseofulvin is excreted unchanged in the feces. Griseofulvin may deposit in basal cells and be transported outward to the epidermis as normal skin grows. This results in a long latency period between the start of treatment and the appearance of signs of improvement. Metabolism/Metabolites: Primarily metabolized in the liver, the major metabolite being 6-methylgriseofulvin and its glucuronide conjugate. Griseofulvin is primarily metabolized to 6-dimethylgriseofulvin and its glucuronide. 6-Dimethylgriseofulvin has been reported as the major urinary metabolite… 4-Dimethylgriseofulvin, previously reported, is absent in humans. Griseofulvin (7-chloro-4,6-dimethoxy-6'-methylgreyrano-2',3,4'-trione) has been identified…
It is primarily metabolized in the liver, with the main metabolites being 6-methylgriseofulvin and its glucuronide conjugate.
Half-life: 9-21 hours
Biological half-life
9-21 hours
The half-life of this drug in plasma is approximately 1 day. Approximately 50% of the oral dose is detectable in urine within 5 days, primarily in the form of metabolites/SRP: 36% detectable in feces within 5 days/.
The half-life of griseofulvin in canine plasma is 47 minutes…

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ADME/Pharmacokinetics: Griseofulvin has a low rate of gastrointestinal absorption which is linearly related to the logarithm of the daily dose. [1]
In rats, drug levels were similar in diverse tissues except the lung and liver, where higher levels were observed after intravenous and oral administration, respectively. [1]
Griseofulvin is metabolized in the liver by demethylation to its microbiologically inactive form 6-desmethylgriseofulvin (6-DMG). Phenobarbital increases the metabolism of GF. [1]
About 50% of an oral dose of [¹⁴C] Griseofulvin was excreted in the urine, where the only major metabolite is 6-DMG. In rat and mouse, 4-DMG is also a major metabolite. [1]
In man, at peak plasma concentrations, the relative proportions of [¹⁴C] Griseofulvin, 6-DMG and other metabolites were 44%, 42% and 14% respectively. [1]
Griseofulvin is deposited in the keratinous layer of the epidermis. In man, its presence can be demonstrated in the outer layers of the stratum corneum within 4-8 hours of administration and in the base of the stratum corneum within 72 hours of administration. [1]

Toxicity Summary
Griseofulvin is an antifungal agent, but the exact mechanism by which it inhibits the growth of dermatophytes is not fully understood. It is currently believed to inhibit fungal cell mitosis and nucleic acid synthesis. It can also bind to α and β tubulin, thereby interfering with the function of the spindle apparatus and cytoplasmic microtubules. In human cells, it binds to keratin; upon reaching the site of fungal action, it binds to fungal microtubules, thereby altering the fungal mitotic process. Hepatotoxicity
Up to 5% of patients treated with griseofulvin may experience transient, mild to moderate elevations in serum transaminase levels, but these abnormalities are usually asymptomatic and return to normal with continued use. Clinically significant hepatotoxicity is rare, with only sporadic case reports. Liver injury is usually cholestatic and typically occurs within the first few months of treatment. Allergic reactions such as fever, rash, and eosinophilia are rare, but griseofulvin can cause allergic reactions. At least one case has been reported of a drug reaction with eosinophilia and systemic symptoms (DRESS) accompanied by elevated serum transaminases after griseofulvin use. Published cases of liver injury caused by griseofulvin are all self-limiting, with a recovery period of 1 to 3 months. Griseofulvin can increase intrahepatic protoporphyrin levels and induce acute porphyria exacerbations in patients with acute intermittent porphyria in remission. Probability score: C (likely a rare cause of clinically significant liver injury). Interactions…In rodents and humans, primidone can accelerate the metabolism of griseofulvin…In mice, griseofulvin, in combination with topical 3-methylcholanthrene, exerts a carcinogenic effect…The effect may be enhanced when alcohol is used concurrently with griseofulvin; furthermore, co-administration with griseofulvin may lead to tachycardia, hyperhidrosis, and flushing.
When used in combination with coumarin or indanedione derivative anticoagulants, the efficacy of these drugs may be reduced; this reduction is thought to be due to stimulation of hepatic microsomal enzyme activity, leading to accelerated anticoagulant metabolism; prothrombin time should be monitored until it reaches a stable level; dose adjustments may be necessary during and after griseofulvin treatment.
For more complete data on drug interactions of griseofulvin (6 types), please visit the HSDB record page.

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Toxicity/Toxicokinetics: The median lethal dose (LD50) of Griseofulvin by intravenous injection in rats is about 400 mg/kg, whereas an intraperitoneal dose of 2 g/kg is tolerated. No acute toxicity was observed in rats and dogs fed GF at doses up to 2 g/kg b.w. daily for several weeks. Single oral doses of 50 g/kg and 10 g/kg b.w. were tolerated by mice and rats respectively. [1]
In rats, severe damage to the seminal epithelium was observed after a few days of treatment at the highest tolerated intraperitoneal doses. A single intravenous injection of 100-200 mg/kg resulted in mitotic arrest in proliferating tissues including bone marrow, intestinal epithelium and transplanted tumors. [1]
In mice, a diet containing 2.5% Griseofulvin for 12 days resulted in a marked decrease (40%) in microsomal protein/g of liver, a 50% reduction in cytochrome P-450, and a 2-fold increase in cytochrome b₅. [1]
Griseofulvin causes porphyria in mouse. Protoporphyrin starts to accumulate in the liver within a few hours after administration, increasing from about 1.5 nmoles/g to an average of 260 nmoles/g wet weight after 3 days, and may reach above 8000 nmoles/g after 2-3 months of feeding. Uncoupling of oxidative phosphorylation in liver mitochondria is observed after 3 weeks of GF feeding when protoporphyrin levels reach 1300 nmoles/g wet weight. [1]
In mice continuously treated with Griseofulvin (0.5-3% in diet for 400-435 days or longer), multiple hepatomas developed. In rats, thyroid tumors developed at treatment levels of 0.2-2.0% in diet. Negative results were obtained in hamsters. [1]
In pregnant rats, Griseofulvin at oral doses of 1250-1500 mg/kg/day caused embryo toxicity, reduced survival, and malformations including tail anomalies, lack of eyes, anal atresia and exencephaly. Doses of 50-500 mg/kg caused fetal death and malformations in a dose-dependent manner. [1]
In mice, Griseofulvin at daily doses of 1000 mg/kg (5 consecutive daily i.p. injections) caused marked increments in the percentage of abnormal sperm (up to 20% or more) at 1 and 4 weeks following the end of exposure. [1]
Griseofulvin was negative in the Salmonella/microsome mutagenicity assay, in the hepatocyte primary culture/DNA repair test, and in bacterial DNA-repair tests using B. subtilis and E. coli. [1]
In the dominant lethal test with male mice given i.p. injection of GF (750-3000 mg/kg), negative results were obtained. [1]

Mutat Res.1988 Mar;195(2):91-126;Int J Cancer.2001 Feb 1;91(3):393-401.

According to the International Agency for Research on Cancer (IARC) of the World Health Organization, griseofulvin is potentially carcinogenic. Griseofulvin is a white to pale milky-white crystalline powder, odorless or almost odorless and tasteless. It sublimes without decomposing at 410°F (210°C). (NTP, 1992) Griseofulvin is an oxaspirocyclic compound produced by Penicillium griseofulvum. It is an oral antifungal drug used to treat infections of the scalp, hair, nails, and skin that are unresponsive to topical treatments. It has antibacterial activity and is a metabolite of Penicillium. It is an organochlorine compound belonging to the 1-benzofuran class of compounds, an oxaspirocyclic compound, and is both an antibiotic and a benzofuran antifungal drug. Griseofulvin is an antifungal antibiotic. It can be taken orally to treat dermatophyte infections. Griseofulvin is a microtubule inhibitor. The physiological action of griseofulvin is achieved by reducing mitosis and inhibiting microtubules. Griseofulvin is a microtubule inhibitor. Its physiological action is achieved by reducing mitosis and inhibiting microtubules. Griseofulvin is an antifungal agent used to treat superficial fungal skin infections such as tinea capitis and tinea pedis. Griseofulvin treatment may cause a transient, mild to moderate increase in serum transaminases, rarely associated with clinically significant acute drug-induced liver injury. Griseofulvin has been reported in Penicillium esculentum, Penicillium griseogreenum, and other microorganisms with relevant data. Griseofulvin is an antifungal drug derived from Penicillium griseofulvin and used to treat fungal infections of the skin and nails. Griseofulvin binds to tubulin, disrupting microtubule function and inhibiting mitosis. Griseofulvin is only present in individuals who have used or taken the drug. It is an antifungal antibiotic. Griseofulvin can be taken orally to treat dermatophyte infections. While griseofulvin has antifungal activity, the exact mechanism by which it inhibits the growth of dermatophytes is unclear. It is currently believed to inhibit fungal cell mitosis and nucleic acid synthesis. It can also bind to α and β tubulin, thereby interfering with the function of the spindle and cytoplasmic microtubules. It binds to keratin in human cells, and upon reaching the site of fungal action, it binds to fungal microtubules, thereby altering the fungal mitotic process.
An antifungal drug used to treat dermatophyte infections.
See also: Ultracrystalline griseofulvin (with subclasses); Microcrystalline griseofulvin (with subclasses). Griseofulvin, ultrafine particles (note moved here).

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Indications
For the treatment of dermatophyte infections of the skin, hair, and nails, including: tinea corporis, tinea pedis, tinea cruris, tinea barbae, seborrheic dermatitis of the infant, or other diseases caused by fungi of the genus Trichophyton or Microsporum.
FDA label

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Mechanism of Action
Griseofulvin is a bacteriostatic agent, but the exact mechanism by which it inhibits the growth of dermatophytes is not fully understood. It is believed to inhibit fungal cell mitosis and nucleic acid synthesis. In addition, it can bind to α-tubulin and β-tubulin, thereby interfering with the function of the spindle and cytoplasmic microtubules. It binds to keratin in human cells, and once it reaches the site of fungal action, it binds to fungal microtubules, thereby altering the fungal mitotic process.
Antimicrobial agent; Griseofulvin inhibits fungal cell mitosis by disrupting the structure of the mitotic spindle, thus arresting metaphase of cell division. It deposits at varying concentrations in keratin precursor cells of the skin, hair, and nails, making keratin resistant to fungal invasion. When infected keratin sheds, it is replaced by healthy tissue.

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Therapeutic uses
Antibiotic, antifungal drug
Griseofulvin is used to treat tinea of the skin, hair, and nails (tinea fungal infections) caused by susceptible Trichophyton, Microsporum, or Epidermophyton, including tinea corporis, tinea pedis, tinea cruris, tinea barbae, tinea capitis, and onychomycosis (nail fungus).
Veterinary Drug: This drug can be used to treat superficial fungal infections caused by Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton interdigitale, etc. Hyoscyamine, sulfur fungi, verrucous fungi, Microsporum, Microsporum canis, Microsporum gypseum…
Drug (Veterinary): Used to treat dermatitis or nail fungus, especially suitable for areas difficult to treat topically (eyes, mouth, nail area) or areas unresponsive to other therapies.
For more complete data on the therapeutic uses of griseofulvin (14 types), please visit the HSDB record page.

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Drug Warnings
Thrush caused by Candida overgrowth has occurred.
Griseofulvin is contraindicated in patients with acute intermittent porphyria or a history of…hepatic cell failure and hypersensitivity to this drug. …Safety during pregnancy has not been established.
Rarely, transient hearing loss has been reported… Long-term treatment may cause paresthesia in the hands and feet… Occasionally, high doses may produce… psychotic symptoms.
Griseofulvin has been reported to cause tachycardia and flushing…
For more complete data on griseofulvin (17 total), please visit the HSDB records page.

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Pharmacodynamics
Griseofulvin is a fungal toxic metabolite of the genus Penicillium. It was the first oral medication used to treat dermatophytes and has been used for over forty years. It is an antifungal agent, and in vitro studies have shown its effectiveness against various Microsporum, Epidermophyton, and Trichophyton fungi. It is ineffective against bacteria or other genera of fungi. After oral administration, griseofulvin deposits in keratin precursor cells, exhibiting a higher affinity for diseased tissue. The drug binds tightly to newly formed keratin, making keratin highly resistant to fungal invasion. Once the keratin-griseofulvin complex reaches the site of action on the skin, it binds to fungal microtubules (tubule proteins), thereby altering fungal mitosis.

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Additional Info: Griseofulvin is a mycotoxin produced by various species of Penicillium including P. griseofulvum, P. janczewski (P. nigricans) and P. patulum. Chemically it is 7-chloro-2',4,6-trimethoxy-6',β-methylspiro[benzofuran-2(3H),1'-[2]-cyclohexene]-3,4-dione with molecular formula C₁₇H₁₇ClO₆ and molecular weight 352.77. [1]
Griseofulvin is a neutral molecule with high lipid solubility and partition coefficient. It is a colorless crystalline powder very slightly soluble in water (10 μg/ml), soluble in methanol (1 mg/ml) and in acetone (10-120 mg/ml). [1]
Griseofulvin has been extensively used in the therapy of dermatophytes by oral administration because of its capacity to concentrate in the keratinous layer of the epidermis and its relatively low toxicity in man. [1]
The mode of action of Griseofulvin on mitotic spindle microtubules involves inhibition of their combination with microtubule-associated proteins (MAPs), unlike colchicine and Vinca alkaloids which bind to tubulin. [1]
At low concentrations, Griseofulvin may disorient MTs; at higher concentrations it can interfere directly with MT assembly. The effect is dose-dependent and reversible. [1]
Griseofulvin has been used as a tool for routine haploidization in Coprinus lagopus and for inducing chromosome segregation in somatic cell genetics. [1]
Griseofulvin is considered to be a drug of low toxicity in man since toxic reactions are virtually absent and no drug-induced suppression of spermatogenesis has been observed after prolonged treatment at therapeutic doses. [1]
GF-induced murine protoporphyria has been used as a model system for human erythropoietic protoporphyria. [1]

C17H17CLO6

352.77

352.071

126-07-8

Griseofulvin;126-07-8

441140

White to off-white solid powder

1.4±0.1 g/cm3

570.4±50.0 °C at 760 mmHg

218-220 °C(lit.)

228.0±29.1 °C

0.0±1.6 mmHg at 25°C

1.583

3.53

0

6

3

24

575

2

C[C@@H]1CC(=O)C=C([C@]12C(=O)C3=C(O2)C(=C(C=C3OC)OC)Cl)OC

DDUHZTYCFQRHIY-RBHXEPJQSA-N

InChI=1S/C17H17ClO6/c1-8-5-9(19)6-12(23-4)17(8)16(20)13-10(21-2)7-11(22-3)14(18)15(13)24-17/h6-8H,5H2,1-4H3/t8-,17+/m1/s1

(2S,6R)-7-chloro-2,4,6-trimethoxy-6-methyl-3H-spiro[benzofuran-2,1-cyclohexan]-2-ene-3,4-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)