Nangia A, Camel E, Berner B, Maibach H
Department of Dermatology, School of Medicine, University of California at San Francisco 94143.
Pharm Res. 1993 Dec;10(12):1756-9. doi: 10.1023/a:1018978232145.
The effects of the application of skin irritants on the in vitro percutaneous absorption of three model compounds of diverse physico-chemical properties, caffeine, indomethacin, and hydrocortisone, were investigated. Norephedrine and imipramine, basic drugs with a known skin irritation potential, were employed to damage the skin. Treatment with norephedrine increased the permeation of caffeine and hydrocortisone by two- to fourfold, while absorption of indomethacin declined an order of magnitude. A similar result was obtained for the effect of treatment with imipramine on transport of caffeine. Pretreatment with imipramine promoted hydrocortisone absorption 10-fold but, unlike norephedrine, did not alter indomethacin permeation. While both treatments in vivo caused an increase (norephedrine > imipramine) in the pH on the surface of skin and after tape-stripping the skin, only norephedrine caused changes in transepidermal water loss in vivo in man. Since imipramine was the more severe irritant as judged by erythema, alterations by irritants of barrier function appeared rather complex.
研究了皮肤刺激剂的应用对三种理化性质不同的模型化合物（咖啡因、吲哚美辛和氢化可的松）体外经皮吸收的影响。去甲麻黄碱和丙咪嗪是已知具有皮肤刺激潜力的碱性药物，被用于损伤皮肤。用去甲麻黄碱处理使咖啡因和氢化可的松的渗透增加了两到四倍，而吲哚美辛的吸收下降了一个数量级。丙咪嗪处理对咖啡因转运的影响也得到了类似结果。用丙咪嗪预处理使氢化可的松的吸收提高了10倍，但与去甲麻黄碱不同的是，它并未改变吲哚美辛的渗透。虽然两种处理在体内均导致皮肤表面及胶带剥离后皮肤的pH值升高（去甲麻黄碱＞丙咪嗪），但只有去甲麻黄碱在人体体内引起了经皮水分流失的变化。由于从红斑情况判断丙咪嗪是更严重的刺激剂，因此刺激剂对屏障功能的改变显得相当复杂。
