Source: Υπουργείο Υγείας (CY) Revision Year: 2015 Publisher: MEDOCHEMIE LTD, 1-10 Constantinoupoleos street, 3011 Limassol, Cyprus
Pharmacotherapeutic group: Antifungals for systemic use
ATC code: D01BA01
Griseofulvin is an antifungal agent acting against dermatophytic fungi used for fungal infections of skin, scalp and nails.
Griseofulvin exerts a fungistatic effect by inhibition of fungal cell mitosis due to distortion of the structure of the mitotic spindle (by interacting with polymerized microtubules). This stops the metaphase part of cell division. The effects of the drug are similar to those of colchicine and vinca alkaloids, but its binding sites on the microtubular protein are distinct. One of the important morphological actions is the production of multinucleate cells as the drug inhibits fungal mitosis.
Griseofulvin is selectively deposited in the keratin precursor cells of skin, hair, and nails, causing resistance to fungal infection. As infected keratin is shed it is thus replaced by healthy tissue.
Following oral administration the principal site of griseofulvin absorption is in the duodenum, although absorption is variable and subject to individual variation. Less than 50% of the oral dose is absorbed. Absorption is enhanced by the presence of fatty foods.
Peak plasma levels of 1 μg/ml–2 μg/ml occur four to eight hours after dosage, and these plasma levels are maintained during long term administration.
In plasma griseofulvin is 84% bound to plasma proteins, predominantly to albumin.
Skin levels of about 12 μg/g–25 μg/g are achieved and maintained during long term therapy. On termination of therapy griseofulvin cannot be detected in skin after two days and cannot be detected in serum after four days.
The elimination half-life of griseofulvin is nine to twenty four hours.
Griseofulvin undergoes extensive hepatic metabolism, with the principal metabolite being 6-demethylgriseofulvin with no microbiological activity.
Unchanged griseofulvin is excreted in the faeces, and to an extent in sweat. The metabolites, either unchanged or as glucuronide conjugates, are excreted in the urine.
Griseofulvin crosses the placental barrier.
Both in vitro and in vivo exposure of mammalian cells to griseofulvin has been shown to result in abnormal segregation of chromosomes following cell division.
During long term trials administering high doses of griseofulvin in food, it was reported that it induced hepatomas in mice, thyroid tumors in rats, but that there was no effect in hamsters. The clinical relevance of these findings with respect to administration in man is unknown, but they contraindicate prophylactic usage of griseofulvin.
Griseofulvin is teratogenic in animals, administration of griseofulvin to rats during pregnancy at high dosages resulted in foetotoxicity and tail deformities. There are case reports of human fetal abnormalities following griseofulvin administration.
Experiments in cows administered griseofulvin 10 mg/kg body weight day for five days resulted in griseofulvin plasma levels comparable to therapeutic levels in man and a milk concentration of griseofulvin 0.16 μg/ml. Although, not directly extrapolated to man, there is the potential risk for nursing infants to ingest significant amounts of griseofulvin.
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