Griseofulvin was isolated from culture broths of Penicillium griseofulvum in 1938 and later also found in culture filtrates of Penicillium nigricans(= P. janczewskii), P. patulum, and other Penicillium species. The structure was determined in 1952. Griseofulvin was first used in plant protection and was introduced to medicine as an antimycotic in 1958.

Solubility

Griseofulvin is soluble in methanol (2.5 g/mL), ethanol (1.5 g/mL), ether, and glacial acetic acid; quite soluble in DMF (150 mg/mL); slightly soluble in chloroform (25 mg/mL), ethyl acetate, acetone (33 mg/mL), and toluene; and insoluble in petroleum ether. The solubility in water is 40 μg/mL.

Mechanism of Action

In addition to the inhibition of protein synthesis resulting from the interference of griseofulvin with guanine during RNA synthesis, there may also be a specific inhibition of chitin synthesis. Chitin is an essential cell-wall constituent in dermatophytes. Inhibition of its synthesis would explain the characteristic morphological changes in the hyphae, called curling, that occur in dermatophytes in the presence of griseofulvine.

Indications

The indications for griseofulvin are dermatophytoses and onychomycoses which do not respond to topical therapy. The optimal daily dose is 5 – 10 mg/kg body weight. The duration of treatment ranges from 3 to 5 weeks for dermatophytoses of the trunk and extremities, and from 5 to 10 weeks for infections of palms, soles, and scalp, but is more than 6 months and even up to 18 months for onychomycoses. Additional topical therapy increases the cure rate and reduces duration of treatment. Due to better tolerability and efficacy, newer antimycotic compounds such as azole antimycotics and allylamines have mostly replaced griseofulvin in the therapy of dermatomycoses and onychomycoses. Griseofulvin is inactive in mycoses caused by fungi other than dermatophytes.