Griseofulvin: It was one of the early antibiotics extracted from Penicillium griseofulvum. However, because of lack of antibacterial activity, little attention was paid to it: clinical utility in dermatophytosis was demonstrated only around 1960. Griseofulvin is active against most dermatophytes, including Epidermophyton, Trichophyton, Microsporum, etc, but not against Candida and other fungi causing deep mycosis. Bacteria are also insensitive. Dermatophytes actively concentrate it: this feature probably accounts for its selective toxicity. Resistance can be induced in vitro and this is associated with loss of concentrating ability. However, emergence of resistance during clinical use is rare. Griseofulvin interferes with mitosis-multinucleated and stunted fungal hyphae result from its action. It also causes abnormal metaphase configurations. However, unlike the typical mitotic inhibitors (colchicine, vinca alkaloids), it does not cause metaphase arrest; rather the daughter r tuclei fail to move apa or move only a sho distance. It does not inhibit polymerization of tubulin (microtubular protein which pulls the chromosomes apa), but binds to polymerized microtubules and somehow disorients them. Pharmacokinetics The absorption of griseofulvin from g.i.t. is somewhat irregular because of its very low water solubility. Absorption is improved by taking it with fats and by microfining the drug paicles; now ultramicrofine paicle preparations from which absorption is still better are available. Griseofulvin gets deposited in keratin forming cells of skin, hair and nails; it is especially concentrated and retained in tinea infected cells Because it is fungistatic and not cidal, the newly formed Keratin is not invaded by the fungus, but the fungus persists in already infected keratin. till it is shed off. Thus, the duration of treatment is dependent upon the site of infection, thickness of infected keratin and its turnover rate. Griseofulvin is used orally only for dermatophytosis . It is ineffective topically. Systemic azoles and terbinafine are equally or more efficacious; preferred now. Majority of localized tinea infections are treated with topical agents. Griseofulvin should be reserved for cases with nail, hair or large body surface involvement. It is effective in athletes foot, but not in pityriasis versicolor. ESSENTIALS FROM MEDICAL PHARMACOLOGY K.D.TRIPATHI SIXTH EDITION PAGE NO:760,761