Experimental Study on Pharmacodynamic Action of Topical Antifungal Agents in the Human Stratum Corneum.
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概要
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The imidazole compound is well established as one of the most valuable agents in the therapy of tinea, because it has a high antifungal activity as well as a broad antifungal spectrum. However, this agent has a little effectiveness for hyperkeratotic type of tinea pedis and manum. With regard to the antifungal activiy of imidazole compound, no correlation has been found between the in vitro MIC (minimum inhibitory concentration) value and the clinical efficacy. This study was undertaken to elucidate the reason why this compound has so littlee effectiveness for hyperkeratotic type of tinea.The study focused on: 1) the influence of human cutaneous horny material on the in vitro antifungal activity (MIC value), 2) the action of absorption and liberation of antifungal agents on the human stratum corneum, and 3) the permeability and retention activity of antifungal agents in the human stratum corneum. In experiment 1, using 4% Sabouraud's dextrose broth with human cutaneous horny material, the MIC value of clotrimazole was higher by 64-256 times than that of control medium. This suggested that the human stratum corneum significantly reduced the antifungal activity of imidazole compound.Based on the growth of dermatophytes on the medium with the sliced human stratum corneum topically treated with antifungal agent, comparative studies were performed on the absorption-liberation (experiment 2) and the permeability-retention activity (experiment 3) of clotrimazole and bifonazole solutions. These revealed that clotrimazole disappeared more rapidly from and was retained much less time in the human stratum corneum than bifonazole.These experiments elucidated a part of the pharmacodynamic action of topical antifungal agents on the human stratum corneum, and experiment 3 seemed to be an especially simple and useful method to evaluate the permeability and the retention activity of agent without the use of any radioactive tracers.
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