Cotovio J, Roguet R, Pion F X, Rougier A, Leclaire J
L'OREAL Advanced Research Center, Aulnay-sous-Bois, France.
Skin Pharmacol. 1996;9(4):242-9. doi: 10.1159/000211421.
We tested the effect of various imidazole derivatives applied topically, on P-450-dependent enzyme activity of a reconstructed epidermis in conditions simulating clinical use. At nontoxic concentrations (determined by a cytotoxicity test based on the reduction of a tetrazolium salt, MTT, by mitochondrial deshydrogenase) econazole and clotrimazole had a biphasic effect on 7-ethoxycoumarin-O-deethylase (ECOD) activity in the epidermis, with induction at low concentrations and inhibition at high concentrations. Dermatological preparations (emulsions, gels) containing imidazole derivatives, which are nontoxic for the epidermis, decreased ECOD activity by about 40% 18 h after topical application. These results are in keeping with in vivo observations after topical application, and stress the value of the reconstructed epidermis for pharmacotoxicological and mechanistic studies of topical agents used in dermatology.
我们在模拟临床使用的条件下，测试了局部应用各种咪唑衍生物对重建表皮中依赖细胞色素P-450的酶活性的影响。在无毒浓度下（通过基于线粒体脱氢酶对四唑盐MTT的还原作用的细胞毒性试验确定），益康唑和克霉唑对表皮中的7-乙氧基香豆素-O-脱乙基酶（ECOD）活性具有双相作用，低浓度时诱导，高浓度时抑制。含有对表皮无毒的咪唑衍生物的皮肤科制剂（乳液、凝胶）在局部应用18小时后使ECOD活性降低约40%。这些结果与局部应用后的体内观察结果一致，并强调了重建表皮在皮肤病学中局部用药的药物毒理学和作用机制研究中的价值。
