Walter K, Kurz H
Walther Straub-Institut für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, FRG.
J Pharm Pharmacol. 1988 Oct;40(10):689-93. doi: 10.1111/j.2042-7158.1988.tb06996.x.
For a series of ten drugs with different physicochemical properties, binding to human skin (epidermis and corium) was determined. Epidermis was obtained by suction blistering, and corium was sliced with a microtome (0.2 mm). Binding experiments were performed in dialysis chambers, containing labelled drug solutions. All drugs investigated were bound to epidermis and corium. With one exception, epidermal drug binding was significantly higher than corial binding. Nevertheless, a good correlation between binding of drugs to both skin fractions could be found. In a range from 10(-7) to 10(-3) mol L-1 binding of drugs to both skin fractions is linear and not saturable. A good correlation was found between binding and lipophilicity of drugs, determined as the partition coefficients between an organic phase (octanol or heptane) and phosphate buffer of pH 7.0. The results show that binding to epidermis and corium is not saturable and depends on lipophilicity of drugs, indicating unspecific binding. Further binding experiments were performed with lipid-depleted tissue. Since drug binding to lipid-depleted samples and control samples differ only to a moderate extent, it is suggested, that tissue lipids play a marginal role on drug binding. Hence, drugs are bound to human skin by other components like proteins.
针对一系列具有不同理化性质的十种药物，测定了它们与人体皮肤（表皮和真皮）的结合情况。通过负压吸疱法获取表皮，用切片机将真皮切成薄片（0.2毫米）。结合实验在含有标记药物溶液的透析室中进行。所有研究的药物均与表皮和真皮结合。除一种药物外，表皮药物结合显著高于真皮结合。然而，药物与两种皮肤组分的结合之间存在良好的相关性。在10⁻⁷至10⁻³摩尔/升的范围内，药物与两种皮肤组分的结合呈线性且不饱和。药物的结合与亲脂性之间存在良好的相关性，亲脂性以有机相（辛醇或庚烷）与pH 7.0的磷酸盐缓冲液之间的分配系数来确定。结果表明，与表皮和真皮的结合是不饱和的，且取决于药物的亲脂性，表明是非特异性结合。对脂质去除组织进行了进一步的结合实验。由于药物与脂质去除样品和对照样品的结合仅在中等程度上有所不同，因此表明组织脂质在药物结合中起次要作用。因此，药物是通过蛋白质等其他成分与人体皮肤结合的。
