Duteil L, Queille C, Poncet M, Ortonne J P, Czernielewski J
Centre de Pharmacologie Clinique Appliquee a la Dermatologie (CPCAD), Nice, France.
Clin Exp Dermatol. 1990 May;15(3):195-9. doi: 10.1111/j.1365-2230.1990.tb02071.x.
The aim of this study was to compare the activities of the two main classes of topical anti-inflammatory drugs in methyl-nicotinate-induced skin inflammation, using a new methodology based on laser-Doppler velocimetry. Six topical non-steroidal anti-inflammatory drugs (NSAIDs) (bufexamac, diclofenac, ibuprofen, indomethacin, phenylbutazone and niflumic acid) and three topical corticosteroids (clobetasol propionate, hydrocortisone and hydrocortisone butyrate) were tested. Drugs were commercially available (except indomethacin) and were applied under occlusion for 4 h to the forearms of 16 healthy male volunteers. Thirty minutes after excess drug removal, skin inflammation was induced by a 1-min application of methyl nicotinate (3 mM). This was repeated 44 h later. Each methyl-nicotinate application was followed by continuous skin blood flow recordings over 1 h. Overall, NSAIDs proved more effective than corticosteroids in inhibiting methyl-nicotinate-induced increases in skin blood flow. Diclofenac and indomethacin showed a potent prolonged inhibitory effect. Different types of activity were observed in the corticosteroid group: (a) At 30 min, hydrocortisone and hydrocortisone butyrate moderately inhibited methyl-nicotinate reactions whereas clobetasol propionate produced no detectable effects; (b) at 44 h, clobetasol propionate produced a significant inhibition whereas hydrocortisone butyrate and hydrocortisone exhibited either weak or no inhibitory action at all. These pharmacodynamic discrepancies between the corticosteroids tested could be related to differences in drug affinity to cutaneous receptors and in vasoconstrictive potency.
本研究的目的是使用基于激光多普勒测速技术的新方法，比较两类主要局部抗炎药物在烟酸甲酯诱导的皮肤炎症中的活性。测试了六种局部非甾体抗炎药（NSAIDs）（丁苯羟酸、双氯芬酸、布洛芬、吲哚美辛、保泰松和氟尼酸）和三种局部皮质类固醇（丙酸氯倍他索、氢化可的松和丁酸氢化可的松）。药物均为市售（吲哚美辛除外），在封闭条件下对16名健康男性志愿者的前臂给药4小时。去除多余药物30分钟后，通过涂抹1分钟的烟酸甲酯（3 mM）诱导皮肤炎症。44小时后重复此操作。每次涂抹烟酸甲酯后，连续记录1小时的皮肤血流情况。总体而言，NSAIDs在抑制烟酸甲酯诱导的皮肤血流增加方面比皮质类固醇更有效。双氯芬酸和吲哚美辛显示出强效且持久的抑制作用。在皮质类固醇组中观察到不同类型的活性：（a）在30分钟时，氢化可的松和丁酸氢化可的松适度抑制烟酸甲酯反应，而丙酸氯倍他索未产生可检测到的效果；（b）在44小时时，丙酸氯倍他索产生显著抑制作用，而丁酸氢化可的松和氢化可的松表现出微弱或根本没有抑制作用。所测试的皮质类固醇之间的这些药效学差异可能与药物对皮肤受体的亲和力和血管收缩效力的差异有关。
