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| Clinical data | |
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| Trade names | Gris-peg, Grifulvin V, others |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682295 |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | Highly variable (25 to 70%) |
| Metabolism | Liver (demethylation andglucuronidation) |
| Eliminationhalf-life | 9–21 hours |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.004.335 |
| Chemical and physical data | |
| Formula | C17H17ClO6 |
| Molar mass | 352.77 g·mol−1 |
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Griseofulvin is anantifungal medication used to treatdermatophytoses (ringworm).[1][2] This includes fungal infections of thenails and scalp, as well as the skin when antifungal creams have not worked.[3] It is taken by mouth.[2]
Common side effects includeallergic reactions,nausea,diarrhea, headache, trouble sleeping, and feeling tired.[2] It is not recommended in people withliver failure orporphyria.[2] Use during or in the months beforepregnancy may result in harm to the baby.[2][3] Griseofulvin works by interfering with fungalmitosis.[1][2]
Griseofulvin was discovered in 1939 from the soil fungusPenicillium griseofulvum.[4][5][6] It is on theWorld Health Organization's List of Essential Medicines.[7]
Griseofulvin is used orally only fordermatophytosis. It is ineffective topically. It is reserved for cases in which topical treatment with creams is ineffective.[8]
Terbinafine given for 2 to 4 weeks is at least as effective as griseofulvin given for 6 to 8 weeks for treatment ofTrichophyton scalp infections. However, griseofulvin is more effective than terbinafine for treatment ofMicrosporum scalp infections.[9][10]
The drug binds totubulin, interfering withmicrotubule function, thus inhibitingmitosis.[11] It binds tokeratin in keratin precursor cells and makes them resistant to fungal infections. The drug reaches its site of action only when hair or skin is replaced by the keratin-griseofulvin complex. Griseofulvin then enters thedermatophyte through energy-dependent transport processes and binds to fungal microtubules. This alters the processing for mitosis and also underlying information for deposition of fungal cell walls.[citation needed]
It is produced industrially by fermenting the fungusPenicillium griseofulvum.[12][13][14]
The first step in the biosynthesis of griseofulvin byP. griseofulvin is the synthesis of the 14-carbon poly-β-keto chain by a type I iterative polyketide synthase (PKS) via iterative addition of 6 malonyl-CoA to an acyl-CoA starter unit. The 14-carbon poly-β-keto chain undergoes cyclization/aromatization, using cyclase/aromatase, respectively, through aClaisen andaldol condensation to form thebenzophenone intermediate. The benzophenone intermediate is thenmethylated viaS-adenosyl methionine (SAM) twice to yield griseophenone C. The griseophenone C is then halogenated at the activated site ortho to thephenol group on the left aromatic ring to form griseophenone B. The halogenated species then undergoes a single phenolic oxidation in both rings forming the two oxygen diradical species. The right oxygen radical shifts alpha to the carbonyl via resonance allowing for a stereospecific radical coupling by the oxygen radical on the left ring forming a tetrahydrofuranone species.[15] The newly formed grisan skeleton with a spiro center is thenO-methylated by SAM to generate dehydrogriseofulvin. Ultimately, a stereoselective reduction of the olefin on dehydrogriseofulvin byNADPH affords griseofulvin.[16][17]
Griseofulvin is found to alter the bile metabolism ofmice by Yokoo et al. 1979. The same team went on to find a similar effect on mice by a chemically unrelated substance,3,5-diethoxycarbonyl-1,4-dihydrocollidine, in Yokoo et al. 1982 and Tsunoo et al. 1987.[18]
