Studies on Griseofulvin. 2. Skin Griseofulvin Levels after Oral Administration. (Studies on Antifungal Agents. VII. Report)
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Relating to the successful use of griseofulvin as a systemic antifungal agent, it has been thought to be important to develop investigation on the drug in the skin. But lack of the method to extract griseofulvin completely from skin may have caused our poor knowledge on this field, even on the skin levels after oral administration.In the present work, skin griseofulvin was extracted with a new method. Each skin sample measured was finely divided, heated with ether-ethanol and filterd. Then the filterd solution was evaporated. In order to isolate griseofulvin in residue, a chromatographic method was convenient. In this work, residue was redissolved in ether, applied on a piece of chromatostrip (made by silica-gel) and developed with methanol. Visualised by means of its ultraviolet fluorescence, the separated griseofulvin was eluded with 10ml of ethanol and measured for fluorescence with Farrand's spectrophotofluorometer.The results obtained were as follows:1) Skin griseofulvin levels in rabbits: orally administered 125mg fine particle griseofulvin showed the peak level of 2.8mcg/g (in epidermis and dermis) and 8.2mcg/g (in subcutaneous fat tissue) at 4 hours after administration. As the levels reduced slowly, the drug was measured in the concentration of 0.9mcg/g (in epidermis and dermis) and 2.9mcg/g (in subcutaneous fat tissue). On the other hand, serum level showed 1.8mcg/ml at 4 hours after administration and a trace at 24 hours.2) Skin griseofulvin levels in human subjects: As it was difficult to obtain skin samples repeatedly and to know nonspecific fluorescence in each subject, only the average skin level at 4 hours after single oral dose of fine particle griseofulvin 500mg was estimated. The estimated level was 12.1 mcg/g (in epidermis and dermis) and 17.5mcg/g (in subcutaneous fat tissue).3) In vitro uptake of griseofulvin measured in the skin sample was 20.3mcg/g (epidermis and dermis) and 36.0mcg/g (subcutaneous fat tissue) in 1% ethanol solution with griseofulvin 0.5mcg/ml.4) Griseofulvin demonstrated a strong affinity to subcutaneous fat tissue in vitro and in vivo. These results, together with many other reports (2, 4, 8, 10, 15, 16), may suggest a possible hypothesis for coexistence of griseofulvin and fat throughout its course from duodenum until stratum coenrum.
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