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Griseofulvin (Gris-PEG; Grifulvin; Fulvicin, Grisactin, Amudane), a naturally occurring spirocyclic compound isolated from some strains of the mold Penicillium griseofulvumam, is an oral antifungal medication approved for use in the treatment of various dermatophytoses (ringworm) such as fungal infections of the nails and skin when antifungal creams did not work. Griseofulvin is a tubulin/microtubule inhibitor that acts by inhibiting cell mitosis via interfering with microtubule function. Griseofulvin is used orally only for dermatophytosis. It is ineffective topically. It is reserved for cases with nail, hair, or large body surface involvement.
Physicochemical Properties
| Molecular Formula | C17H17CLO6 | |
| Molecular Weight | 352.77 | |
| Exact Mass | 352.071 | |
| CAS # | 126-07-8 | |
| Related CAS # | Griseofulvin;126-07-8 | |
| PubChem CID | 441140 | |
| Appearance | White to off-white solid powder | |
| Density | 1.4±0.1 g/cm3 | |
| Boiling Point | 570.4±50.0 °C at 760 mmHg | |
| Melting Point | 218-220 °C(lit.) | |
| Flash Point | 228.0±29.1 °C | |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C | |
| Index of Refraction | 1.583 | |
| LogP | 3.53 | |
| Hydrogen Bond Donor Count | 0 | |
| Hydrogen Bond Acceptor Count | 6 | |
| Rotatable Bond Count | 3 | |
| Heavy Atom Count | 24 | |
| Complexity | 575 | |
| Defined Atom Stereocenter Count | 2 | |
| SMILES | C[C@@H]1CC(=O)C=C([C@]12C(=O)C3=C(O2)C(=C(C=C3OC)OC)Cl)OC |
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| InChi Key | DDUHZTYCFQRHIY-RBHXEPJQSA-N | |
| InChi Code | 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 | |
| Chemical Name | (2S,6R)-7-chloro-2,4,6-trimethoxy-6-methyl-3H-spiro[benzofuran-2,1-cyclohexan]-2-ene-3,4-dione | |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
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| ln Vivo |
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| Animal Protocol |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Poorly absorbed from GI ranging from 25 to 70% of an oral dose. Absorption is significantly enhanced by administration with or after a fatty meal. IN RATS GIVEN ORAL DOSES OF 100 MG/KG BODY WT (36)CL-GRISEOFULVIN, 10% OF ACTIVITY WAS FOUND IN URINE AFTER 24 HR & 4% DURING 24-48 HR. ...IN ANOTHER STUDY, WITHIN 24-HR PERIOD ONLY 0.14% OF SIMILAR ORAL DOSES IN RATS WAS FOUND IN URINE, & 16% WAS RECOVERED IN FECES. FOLLOWING ITS IV INJECTION GRISEOFULVIN WAS DISTRIBUTED EVENLY THROUGHOUT TISSUES, ALTHOUGH HIGHER LEVELS WERE FOUND IN SKIN & LUNG. Microsize - variable, ranging from 25 to 70% of an oral dose. Ultramicrosize - Almost completely absorbed. Absorption is significantly enhanced by administration with or after a fatty meal. Griseofulvin is deposited in varying concentrations in the keratin layer of the skin, hair, and nails. It can be detected in the stratum corneum of the skin within a few hours following administration. Only a very small fraction of an oral dose is distributed in the body fluids and tissues. Elimination: Renal. less than 1% of a dose is excreted as unchanged drug in the urine. Approximately 36% of griseofulvin is excreted unchanged in the feces. GRISEOFULVIN IS PROBABLY DEPOSITED IN BASAL CELLS AND IS CARRIED OUTWARDS INTO EPIDERMIS AS NORMAL SKIN GROWTH PROCEEDS. THIS...MAKES FOR LONG LATENCY FROM TIME MEDICATION IS BEGUN UNTIL EVIDENCE OF IMPROVEMENT OCCURS. Metabolism / Metabolites Primarily hepatic with major metabolites being 6-methyl-griseofulvin and its glucuronide conjugate. Griseofulvin is mainly metabolized to 6-dimethylgriseofulvin and its glucuronide. ...IT HAS BEEN REPORTED THAT 6-DEMETHYLGRISEOFULVIN IS THE MAJOR URINARY METABOLITE...IN MAN, THE PREVIOUSLY REPORTED 4-DEMETHYL-GRISEOFULVIN WAS ABSENT. GRISEOFULVIC ACID (7-CHLORO-4,6-DIMETHOXY-6'-METHYLGRISAN-2',3,4'-TRIONE) WAS IDENTIFIED... Primarily hepatic with major metabolites being 6-methyl-griseofulvin and its glucuronide conjugate. Half Life: 9-21 hours Biological Half-Life 9-21 hours DRUG HAS A HALF-LIFE IN PLASMA OF ABOUT 1 DAY, & APPROX 50% OF ORAL DOSE CAN BE DETECTED IN THE URINE WITHIN 5 DAYS, MOSTLY IN THE FORM OF METABOLITES /SRP: 36% IN THE FECES WITHIN 5 DAYS/. The half-life of griseofulvin in canine plasma was found to be 47 minutes ... . |
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| Toxicity/Toxicokinetics |
Toxicity Summary Griseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis. Hepatotoxicity Transient mild-to-moderate elevations in serum aminotransferase levels occur in up to 5% of patients treated with griseofulvin, but these abnormalities are usually asymptomatic and resolve even with continuation of the medication. Clinically apparent hepatotoxicity is rare and only isolated case reports have been published. The liver injury is typically cholestatic and usually arises within the first few months of therapy. Signs of hypersensitivity such as fever, rash and eosinophilia are rare but griseofulvin can include hypersensitivity reactions and at least one case of DRESS syndrome accompanied by serum aminotransferase elevations has been reported with its use. Published cases of griseofulvin induced liver injury have all been self-limited, recovery requiring 1 to 3 months. Griseofulvin can increase intrahepatic levels of protoporphyrin and induce acute attacks of porphyria in patients with acute intermittent porphyria in remission. Likelihood score: C (probable rare cause of clinically apparent liver injury). Interactions ...METABOLISM /OF GRISEOFULVIN/ IS ACCELERATED BY...PRIMIDONE IN RATS AND MAN... GRISEOFULVIN ACTED AS A COCARCINOGEN WITH SKIN APPLICATIONS OF 3-METHYLCHOLANTHRENE IN MICE... Effects may be potentiated when alcohol is used concurrently with griseofulvin; also, concurrent use with griseofulvin may result in tachycardia, diaphoresis, and flushing. /Coumarin- or indandione-derivative anticoagulants/ effects, may be decreased when these agents are used concurrently with griseofulvin; decrease is thought to be due to accelerated metabolism of anticoagulants secondary to stimulation of hepatic microsomal enzyme activity; prothrombin time should be monitored until a stable level is maintained; dosage adjustments may be necessary during and after griseofulvin therapy. For more Interactions (Complete) data for GRISEOFULVIN (6 total), please visit the HSDB record page. |
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| References | Mutat Res.1988 Mar;195(2):91-126;Int J Cancer.2001 Feb 1;91(3):393-401. | ||
| Additional Infomation |
Griseofulvin can cause cancer according to The World Health Organization's International Agency for Research on Cancer (IARC). Griseofulvin appears as white to pale cream-colored crystalline powder. Odorless or almost odorless. Tasteless. Sublimes without decomposition at 410 °F. (NTP, 1992) Griseofulvin is an oxaspiro compound produced by Penicillium griseofulvum. It is used by mouth as an antifungal drug for infections involving the scalp, hair, nails and skin that do not respond to topical treatment. It has a role as an antibacterial agent and a Penicillium metabolite. It is an organochlorine compound, a member of 1-benzofurans, an oxaspiro compound, an antibiotic antifungal drug and a benzofuran antifungal drug. An antifungal antibiotic. Griseofulvin may be given by mouth in the treatment of tinea infections. Griseofulvin is a Tubulin Inhibiting Agent. The physiologic effect of griseofulvin is by means of Decreased Mitosis, and Microtubule Inhibition. Griseofulvin is a Tubulin Inhibiting Agent. The physiologic effect of griseofulvin is by means of Decreased Mitosis, and Microtubule Inhibition. Griseofulvin is a fungistatic agent used to treat superficial fungal skin infections such as tinea capitis and pedis. Griseofulvin therapy can cause transient mild-to-moderate serum aminotransferase elevations and has very rarely been linked to clinically apparent acute drug induced liver injury. Griseofulvin has been reported in Penicillium aethiopicum, Penicillium canescens, and other organisms with data available. Griseofulvin is an antifungal agent derived from the mold Penicillium griseofulvum that is used to treat fungal infections of the skin and nails. Griseofulvin binds to tubulin, disrupting microtubule function and inhibiting mitosis. Griseofulvin is only found in individuals that have used or taken this drug. It is an antifungal antibiotic. Griseofulvin may be given by mouth in the treatment of tinea infections. Griseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis. An antifungal agent used in the treatment of TINEA infections. See also: Griseofulvin, ultramicrocrystalline (has subclass); Griseofulvin, microcrystalline (has subclass); Griseofulvin, ultramicrosize (annotation moved to). Drug Indication For the treatment of ringworm infections of the skin, hair, and nails, namely: tinea corporis, tinea pedis, tinea cruris, tinea barbae, cradle cap or other conditions caused by Trichophyton or Microsporum fungi. FDA Label Mechanism of Action Griseofulvin is fungistatic, however the exact mechanism by which it inhibits the growth of dermatophytes is not clear. It is thought to inhibit fungal cell mitosis and nuclear acid synthesis. It also binds to and interferes with the function of spindle and cytoplasmic microtubules by binding to alpha and beta tubulin. It binds to keratin in human cells, then once it reaches the fungal site of action, it binds to fungal microtubes thus altering the fungal process of mitosis. Fungistatic; griseofulvin inhibits fungal cell mitosis by causing disruption of the mitotic spindle structure, thereby arresting the metaphase of cell division. It is deposited in varying concentrations in the keratin precursor cells of skin, hair, and nails, rendering the keratin resistant to fungal invasion. As the infected keratin is shed, it is replaced with healthy tissue. Therapeutic Uses Antibiotics, Antifungal GRISEOFULVIN IS USED IN THE TREATMENT OF TINEAS (RINGWORM INFECTIONS) OF THE SKIN, HAIR & NAILS--TINEA CORPORIS, TINEA PEDIS, TINEA CRURIS, TINEA BARBAE, TINEA CAPITIS & TINEA UNGUIUM (ONYCHOMYCOSIS) CAUSED BY SUSCEPTIBLE SPECIES OF TRICHOPHYTON, MICROSPORUM, OR EPIDERMOPHYTON. MEDICATION (VET): DRUG IS USEFUL IN TREATMENT OF SUPERFICIAL FUNGUS INFECTIONS CAUSED BY TRICHOPHYTON MENTAGROPHYTES, RUBRUM, INTERDIGITALE, SCHOENLEINI, SULPHUREUM AND VERRUCOSUM, AND MICROSPORUM AND OVINI, CANIS, AND GYPSEUM... MEDICATION (VET): TO TREAT RINGWORM OF SKIN OR NAILS ESPECIALLY THOSE AREAS DIFFICULT TO TREAT LOCALLY (EYE, MOUTH, NAIL AREAS), OR THOSE REFRACTORY TO OTHER THERAPY. For more Therapeutic Uses (Complete) data for GRISEOFULVIN (14 total), please visit the HSDB record page. Drug Warnings ORAL THRUSH DUE TO CANDIDAL OVERGROWTH HAS...OCCURRED. GRISEOFULVIN...IS CONTRAINDICATED IN PATIENTS WITH ACUTE INTERMITTENT PORPHYRIA OR A HISTORY OF.../IT/, HEPATOCELLULAR FAILURE, AND HYPERSENSITIVITY TO THE DRUG. ... SAFE USE...DURING PREGNANCY HAS NOT BEEN ESTABLISHED. RARELY, TRANSIENT DIMINUTION OF HEARING HAS OCCURRED...PARESTHESIAS OF HANDS AND FEET HAS FOLLOWED EXTENDED THERAPY... OCCASIONALLY, LARGE DOSES HAVE PRODUCED...PSYCHOTIC SYMPTOMS. GRISEOFULVIN HAS BEEN REPORTED TO CAUSE TACHYCARDIA AND FLUSHING... For more Drug Warnings (Complete) data for GRISEOFULVIN (17 total), please visit the HSDB record page. Pharmacodynamics Griseofulvin is a mycotoxic metabolic product of Penicillium spp. It was the first available oral agent for the treatment of dermatophytoses and has now been used for more than forty years. Griseofulvin is fungistatic with in vitro activity against various species of Microsporum Epidermophyton, and Trichophyton. It has no effect on bacteria or on other genera of fungi. Following oral administration, griseofulvin is deposited in the keratin precursor cells and has a greater affinity for diseased tissue. The drug is tightly bound to the new keratin which becomes highly resistant to fungal invasions. Once the keratin-Griseofulvin complex reaches the skin site of action, it binds to fungal microtubules (tubulin) thus altering fungal mitosis. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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. Injection Formulations (e.g. IP/IV/IM/SC) 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). 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) Oral Formulations 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). 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8347 mL | 14.1735 mL | 28.3471 mL | |
| 5 mM | 0.5669 mL | 2.8347 mL | 5.6694 mL | |
| 10 mM | 0.2835 mL | 1.4174 mL | 2.8347 mL |