Action

Microbiology - Griseofulvin is fungistatic with in vitro activity against various species of Microsporum, Epidermophyton and Trichophyton. It has no effect on bacteria or other genera of fungi.

Pharmacokinetics - 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.

The efficiency of gastrointestinal absorption of ultramicrocrystalline griseofulvin is approximately one and one-half times that of the conventional microsize griseofulvin. This factor permits the oral intake of two-thirds as much ultramicrocrystalline griseofulvin as the microsize form. However, there is currently no evidence that this lower dose confers any significant clinical differences with regard to safety and/or efficacy.

In a bioequivalence study conducted in healthy volunteers (N=24) in the fasted state, 250 mg ultramicrocrystalline griseofulvin tablets were compared with 250 mg ultramicrocrystalline griseofulvin tablets that were physically altered (crushed) and administered with applesauce. The 250 mg ultramicrocrystalline griseofulvin tablets were found to be bioequivalent to the physically altered (crushed) 250 mg ultramicrocrystalline griseofulvin tablets (See Table 1).

Table 1: Mean (± SD) of the Pharmacokinetic Parameters for Griseofulvin administered in applesauce as a Single Dose of GRIS-PEG® (griseofulvin) 250-mg Tablets Uncrushed and Crushed to fasted
Healthy Volunteers (N=24)

Animal Toxicology - Chronic feeding of griseofulvin, at levels ranging from0.5%-2.5% of the diet resulted in the development of liver tumors in several strains of mice, particularly in males. Smaller particle sizes result in an enhanced effect. Lower oral dosage levels have not been tested. Subcutaneous administration of relatively small doses of griseofulvin once a week during the first three weeks of life has also been reported to induce hepatomata in mice. Thyroid tumors, mostly adenomas but some carcinomas, have been reported in male rats receiving griseofulvin at levels of 2.0%, 1.0% and 0.2% of the diet, and in female rats receiving the two higher dose levels. Although studies in other animal species have not yielded evidence of tumorigenicity, these studies were not of adequate design to forma basis for conclusion in this regard. In subacute toxicity studies, orally administered griseofulvin produced hepatocellular necrosis in mice, but this has not been seen in other species. Disturbances in porphyrin metabolismhave been reported in griseofulvin-treated laboratory animals. Griseofulvin has been reported to have a colchicine-like effect on mitosis and cocarcinogenicity with methylcholanthrene in cutaneous tumor induction in laboratory animals.

Last reviewed on RxList: 2/18/2008
This monograph has been modified to include the generic and brand name in many instances.