Terbinafine (Tbf) is a well-established anti-fungal agent used for management of a variety of dermal conditions including ringworm and athlete's foot. Both the biochemical mechanism of Tbf fungicidal action (based on squalene epoxidase inhibition) and the target region for Tbf in vivo (the stratum corneum (SC)) are well determined. However, the biochemical and pharmacokinetic approaches used to evaluate Tbf biochemistry provide no biophysical information about molecular level physical changes in the SC upon Tbf binding. Such information is necessary for improved drug and formulation design. IR spectroscopic methods were used to evaluate the effects of Tbf on keratin structure in environments commonly used in pharmaceutics to mimic those in vivo. The Amide I and II spectral regions (1500-1700 cm-1) provided an effective means to monitor keratin secondary structure changes, while a Tbf spectral feature near 775 cm-1 provides a measure of relative Tbf levels in skin. Interaction of Tbf with the SC induced substantial β-sheet formation in the keratin, an effect which was partially reversed both by ethanol washing and by exposure to high relative humidity. The irreversibility suggests the presence of a Tbf reservoir (consistent with kinetic studies), permitting the drug to be released in a controlled manner into the surrounding tissue.

中文翻译：

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FT-IR研究特比萘芬与角质层成分的相互作用。

特比萘芬（Tbf）是一种行之有效的抗真菌剂，可用于管理多种皮肤病，包括癣和脚癣。Tbf杀真菌作用的生化机制（基于角鲨烯环氧酶抑制作用）和体内Tbf的目标区域（角质层（SC））都得到了很好的确定。但是，用于评估Tbf生物化学的生化和药代动力学方法没有提供有关Tbf结合后SC中分子水平物理变化的生物物理信息。这样的信息对于改进药物和制剂设计是必要的。红外光谱法用于评估Tbf对药物仿生体内常用环境中角蛋白结构的影响。酰胺I和II光谱区域（1500-1700 cm-1）提供了一种有效的方法来监测角蛋白二级结构的变化，而775 cm-1附近的Tbf光谱特征可测量皮肤中相对Tbf的水平。Tbf与SC的相互作用在角蛋白中诱导了实质性的β-折叠形成，这种作用在乙醇洗涤和暴露于高相对湿度下均被部分逆转。不可逆性表明存在Tbf储库（与动力学研究一致），从而允许药物以受控方式释放到周围组织中。通过乙醇洗涤和暴露于高相对湿度都部分抵消了这种作用。不可逆性表明存在Tbf储库（与动力学研究一致），从而允许药物以受控方式释放到周围组织中。通过乙醇洗涤和暴露于高相对湿度都部分抵消了这种作用。不可逆性表明存在Tbf储库（与动力学研究一致），从而允许药物以受控方式释放到周围组织中。