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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Evaluation of fungicidal action in vitro and in a skin model considering the influence of penetration kinetics of various standard antimycotics.

Ciclopiroxolamine (Loprox) was the first representative of hydroxpyridones to be developed as a topical antifungal. In the microtitration test and in a skin model using excised skin prices of slaughtered pigs, the fungistatic and fungicidal activity as well as the penetration kinetics of ciclopiroxolamine and ciclopirox were compared with those of the azole compounds bifonazole, clotrimazole, econazole, miconazole, oxiconazole, and tioconazole, and with other antimycotics such as naftifine, sulbentine, tolciclate, and tolnaftate. Clotrimazole had an in vitro inhibitory activity superior to that of the hydroxypyridone ciclopiroxolamine; the latter compound, however, exhibited faster penetration and higher inhibitory or fungicidal activity than the azoles and other antimycotics in the pig skin model. Studies of cream formulations with antimycotics at the bottom layer of the stratum corneum (close to the stratum granulosum) showed that ciclopiroxolamine cream had the most prominent inhibitory effect (93%) and the highest fungicidal activity (98%). The other antimycotics tested exhibited growth inhibition rates of 50% or less and lower fungicidal rates. Inoculated pig skin was treated with lacquer formulations to show that ciclopirox completely inhibited the growth of Trichophyton mentagrophytes, whereas the clotrimazole-treated samples allowed only 0.47% growth. The fungicidal activity of lacquer formulations was 99% for ciclopirox and around 90% for most of the azoles on the pig skin model. The necessity of models tackling the complex penetration kinetics in human skin was discussed.[1]


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