Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C17H17ClO6 |
Molecular Weight | 352.766 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC(OC)=C2C(=O)[C@]3(OC2=C1Cl)[C@H](C)CC(=O)C=C3OC
InChI
InChIKey=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
Molecular Formula | C17H17ClO6 |
Molecular Weight | 352.766 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionSources: http://www.drugbank.ca/drugs/DB00400Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050475s057lbl.pdf
Sources: http://www.drugbank.ca/drugs/DB00400
Curator's Comment: Description was created based on several sources, including
http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/050475s057lbl.pdf
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. 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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Candida albicans growth Sources: https://www.ncbi.nlm.nih.gov/pubmed/26900659 |
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Target ID: Aspergillus fumigatus growth Sources: https://www.ncbi.nlm.nih.gov/pubmed/26900659 |
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Target ID: Fungi growth Sources: https://www.ncbi.nlm.nih.gov/pubmed/26369643 |
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Target ID: P87066 Gene ID: NA Gene Symbol: TUB1 Target Organism: Candida albicans (Yeast) Sources: http://www.drugbank.ca/drugs/DB00400 |
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Target ID: Staphylococcus aureus growth Sources: https://www.ncbi.nlm.nih.gov/pubmed/25103127 |
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Target ID: P10875 Gene ID: NA Gene Symbol: TUB2 Target Organism: Candida albicans (Yeast) Sources: http://www.drugbank.ca/drugs/DB00400 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | GRIS-PEG Approved UseGris-PEG® (griseofulvin ultramicrosize) is indicated for the treatment of the following ringworm
infections; tinea corporis (ringworm of the body), tinea pedis (athlete’s foot), tinea cruris (ringworm of
the groin and thigh), tinea barbae (barber’s itch), tinea capitis (ringworm of the scalp), and tinea unguium
(onychomycosis, ringworm of the nails), when caused by one or more of the following genera of fungi:
Trichophyton rubrum, Trichophyton tonsurans, Trichophyton mentagrophytes, Trichophyton
interdigitalis,Trichophyton verrucosum, Trichophyton megnini, Trichophyton gallinae, Trichophyton
crateriform, Trichophyton sulphureum, Trichophyton schoenleini, Microsporum audouini, Microsporum
canis, Microsporum gypseum and Epidermophyton floccosum Launch Date1975 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
629.77 ng/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1310.28 ng/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1.39 μg/mL |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
1.25 μg/mL |
330 mg single, oral dose: 330 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
600.61 ng/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
18827.7 ng × h/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
20735.2 ng × h/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
25.9 ng × h/mL |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
21.1 μg × h/mL |
330 mg single, oral dose: 330 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
8618.89 ng × h/mL |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN unknown | Homo sapiens population: HEALTHY age: UNKNOWN sex: UNKNOWN food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
10.716 h |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
9.043 h |
250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
10.7 h |
500 mg single, oral dose: 500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
10.3 h |
330 mg single, oral dose: 330 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
16% |
330 mg single, oral dose: 330 mg route of administration: Oral experiment type: SINGLE co-administered: |
GRISEOFULVIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://doi.org/10.1080/10837450902891550 Page: 12.0 |
yes | |||
Page: 7.0 |
yes | |||
Page: 7.0 |
yes | |||
Page: 7.0 |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Hepatocarcinogenicity of griseofulvin following parenteral administration to infant mice. | 1967 Oct |
|
[Teratogenic effect of griseofulvin-forte on rat fetus]. | 1969 Jan |
|
Skin temperature changes in Raynaud's disease after griseofulvin. | 1970 Mar |
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[Studies in 25 patients with progressive systemic scleroderma treated by long-term administration of griseofulvin]. | 1973 Jun 20 |
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[Central nervous symptoms as side effects of mycosis treatment with griseofulvin]. | 1974 Oct 30 |
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Letter: Psychotic symptoms with griseofulvin. | 1974 Sep 9 |
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[Case of epilepsy caused by griseofulvin]. | 1977 Oct |
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Thyroid tumours in rats and hepatomas in mice after griseofulvin treatment. | 1978 Aug |
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Effect of Griseofulvin on 5-aminolevulinate synthase and on ferrochelatase in mouse liver neoplastic nodules. | 1981 Apr |
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[Hepatoma after long-term administration of griseofulvin]. | 1981 May |
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Bile secretion and liver microsomal mixed function oxidase system in mice with griseofulvin-induced hepatic protoporphyria. | 1983 May |
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Mallory body formation runs parallel to gamma-glutamyl transferase induction in hepatocytes of griseofulvin-fed mice. | 1983 Nov-Dec |
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Screening for new compounds with antiherpes activity. | 1984 Oct |
|
Changes in the cytokeratin intermediate filament cytoskeleton associated with Mallory body formation in mouse and human liver. | 1987 Nov-Dec |
|
Griseofulvin-induced neuropathy. | 1990 Jan 27 |
|
Isolated erythroid hypoplasia and renal insufficiency induced by long-term griseofulvin therapy. | 1990 Nov |
|
[A case of mixed connective tissue disease exacerbated by griseofulvin complicating aseptic meningo-encephalitis and disseminated intravascular coagulation]. | 1990 Oct |
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Kawasaki-like syndrome associated with griseofulvin treatment. | 1993 Jul |
|
Serial light and electron microscopic changes in renal glomeruli in mice fed griseofulvin. | 1993 May-Jun |
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Disturbance of keratin homeostasis in griseofulvin-intoxicated mouse liver. | 1993 Nov |
|
A double blind study of itraconazole vs griseofulvin in patients with tinea pedis and tinea manus. | 1994 Apr 13 |
|
Proximal myopathy associated with griseofulvin therapy. | 1994 Jan |
|
An unusual case of severe griseofulvin-alcohol interaction. | 1994 Jul |
|
Up-regulation of CYP2A5 expression by porphyrinogenic agents in mouse liver. | 1995 Apr |
|
Nephrotic syndrome related to systemic lupus erythematosus after griseofulvin therapy. | 1995 Aug |
|
Myositis associated with griseofulvin therapy. | 1995 Oct |
|
Susceptibility to hepatotoxicity in transgenic mice that express a dominant-negative human keratin 18 mutant. | 1996 Aug 15 |
|
Experimental Mallory body formation is accompanied by modulation of the expression of multidrug-resistance genes and their products. | 1996 Jul |
|
Griseofulvin and fluvoxamine interactions with the metabolism of theophylline. | 1997 Feb |
|
Regulation of CYP 2 A 5 induction by porphyrinogenic agents in mouse primary hepatocytes. | 1997 Jan |
|
Hepatic injury during ketoconazole therapy in patients with onychomycosis: a controlled cohort study. | 1997 Jan |
|
Differential xenobiotic induction of CYP2A5 in mouse liver, kidney, lung, and olfactory mucosa. | 1998 Aug |
|
Cell wall active antifungal compounds produced by the marine fungus Hypoxylon oceanicum LL-15G256. III. Biological properties of 15G256 gamma. | 1998 Mar |
|
Inhibition of PPAR alpha/RXR alpha-mediated direct hyperplasia pathways during griseofulvin-induced hepatocarcinogenesis. | 1998 May 1 |
|
Synthesis and biological activity of peptide derivatives of iodoquinazolinones/nitroimidazoles. | 2008 Apr 24 |
|
A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine. | 2008 Aug |
|
Manifestation of psychiatric behaviors in a mouse model of griseofulvin-induced hepatic porphyria. | 2008 Dec |
|
[Antimycotic therapy of Tinea pedis and other foot mycoses]. | 2008 Jul |
|
Epidermal growth factor receptor ligands in murine models for erythropoietic protoporphyria: potential novel players in the progression of liver injury. | 2009 Feb 16 |
|
Tinea capitis: diagnostic criteria and treatment options. | 2009 Jan-Feb |
|
Tinea capitis: diagnostic criteria and treatment options. | 2009 Sep-Oct |
|
Synthesis, in vitro antibacterial and antifungal evaluations of new alpha-hydroxyphosphonate and new alpha-acetoxyphosphonate derivatives of tetrazolo [1, 5-a] quinoline. | 2010 Mar |
|
Synthesis and the selective antifungal activity of 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine derivatives. | 2010 May |
|
Novel insights into changes in biochemical properties of keratins 8 and 18 in griseofulvin-induced toxic liver injury. | 2010 Oct |
|
Synthesis and characterization of some new quinoline based derivatives endowed with broad spectrum antimicrobial potency. | 2012 Nov 15 |
|
Green synthesis and anti-infective activities of fluorinated pyrazoline derivatives. | 2012 Sep 1 |
|
The anti-mitotic drug griseofulvin induces apoptosis of human germ cell tumor cells through a connexin 43-dependent molecular mechanism. | 2013 Apr |
|
An efficient domino reaction in ionic liquid: synthesis and biological evaluation of some pyrano- and thiopyrano-fused heterocycles. | 2013 Mar 15 |
|
Complexity generation in fungal polyketide biosynthesis: a spirocycle-forming P450 in the concise pathway to the antifungal drug griseofulvin. | 2013 Oct 18 |
|
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. | 2015 May 18 |
Patents
Sample Use Guides
Adults: Daily administration of 375 mg (as a single dose or in divided doses) will give a satisfactory response in most patients with tinea corporis, tinea cruris, and tinea capitis. For those fungal infections more difficult to eradicate, such as tinea pedis and tinea unguium, a divided dose of 750 mg is recommended.
Pediatric Use: Approximately 7.3 mg per kg of body weight per day of ultramicrosize griseofulvin is an
effective dose for most pediatric patients. On this basis, the following dosage schedule is suggested:
16-27 kg: 125 mg to 187.5 mg daily.
over 27 kg: 187.5 mg to 375 mg daily
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25103127
Griseofulvin displayed strong inhibitory effects on the growth of A. solani and S. aureus with MIC of 3.13 uM for each.
Substance Class |
Chemical
Created
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on
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on
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Record UNII |
32HRV3E3D5
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C514
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NDF-RT |
N0000008732
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LIVERTOX |
NBK548177
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WHO-ATC |
D01AA08
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WHO-VATC |
QD01BA01
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EPA PESTICIDE CODE |
471400
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WHO-VATC |
QD01AA08
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CFR |
21 CFR 520.1100
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WHO-ATC |
D01BA01
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NDF-RT |
N0000175085
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WHO-ESSENTIAL MEDICINES LIST |
6.3
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NDF-RT |
N0000175848
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91077
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C65819
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34533
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GRISEOFULVIN
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100000092791
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875
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217398
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32HRV3E3D5
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DB00400
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441140
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126-07-8
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27779
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griseofulvin
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5021
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204-767-4
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GRISEOFULVIN
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PRIMARY | Description: White to pale cream powder; almost odourless. Solubility: Very slightly soluble in water; slightly soluble in ethanol (~750 g/l) TS; freely soluble in tetrachloroethane R. Category: Antifungal. Storage: Griseofulvin should be kept in a well-closed container. Additional information: The particles of Griseofulvin are generally up to 5 .MU.m in maximum dimension, although occasionally larger particles may be present that exceed 30 μm.Definition: Griseofulvin contains not less than 97.0% and not more than 102.0% of C17H17ClO6, calculated with reference to the dried substance. | ||
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m5854
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PRIMARY | Merck Index | ||
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SUB07966MIG
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1331
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D006118
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32HRV3E3D5
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755822
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CHROMATOGRAPHIC PURITY (HPLC/UV)
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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