Fundamental Studies on Antifungal Activity of Griseofulvin

III. On Curative and Fungicidal Effects of Griseofulvin in Vivo and its Hemolytic Action

Abstract

A previous paper describes the antimicorobial activity of griseofulvin against various pathogenic microorganisms, especially against dermatophytes, combined action with other antifungal agents, and drug resistance, all in vitro.
This note reports the antifungal activity in vivo and hemolytic action of this drug, Spores of Trichoplhyton mentagrophytes was inoculated to depilated skin on the back of guinea pigs (5 animals in each group) and suspension in a 1% of carboxy-methylcellulose saline solution of griscoflvin was applied orally once daily for 10 day, 5 days after the inoculation. In order to ascertain the minimal effective dose, in various doses of each group of animals was given daily 40, 20, 10, 5 mg per Kg of body weight. Animals were observed as to the redness and scaling at inoculated local sites.
The groups of 40 mg/Kg and 20 mg/Kg showed slight symptoms as early as the third day after the start of treatment and 8-10 days later the lesions were almost or completely cured. But, it was to be noted that, in a few of them even after 10 days the local sites proved still culturally positive for T. mentagrophytes in the group of 10mg/Kg, a slight improvement was noted on the fourth to fifth day and on the tenth day the lesions were almost cured, the grade of improvement being not so conspicuous as in the former groups. In the group of 5 mg/Kg, no improvment was noted during the treatment.
Topical administration was tested with a 0.5% and 1 % of griseofulvin ointments (hydrophilic pjastibase was used) on experimental trichophytosis. A 1 % griseofulvin ointment proved effective. cure rate being about 75%, whereas a 0.5% ointhment showed no effect.
In an attempt to know the mode of action of griseofulvin on trichophyton, the following test was done : the infected scals of guinea pigs enclosed in a capsule of stainless steel wire, was put in a 0.5 % griseofulvin solution, then the material was picked out at definite intervals and tested for the growth of the fungus on Sabouraud's dextrose agar. This experiment showed that griseofulvin was not fungicidal even at higher concentration, because the fungus grew well after the long lasting contact (24 hours). However, it was to be noted that the obtained from a 0.5% of griseofulvin solution after 24 hours showed marked morphological changes both macroscopically and microscopically.
Hemolytic action of griseofulvin on human and rabbit erythrocytes were tested in vitro. Complete hemolysis was observed as to both erythrocytes in 200 mcg/ml or more of the drug solution, but not in 100 mcg/ml or less, whereas other antifungal agents (i.e., nystatin) showed more toxic effects.