Wilhelm K P, Surber C, Maibach H I
Department of Dermatology, School of Medicine, University of California San Francisco 94143-0989.
J Invest Dermatol. 1991 Nov;97(5):927-32. doi: 10.1111/1523-1747.ep12491710.
The influence of sodium lauryl sulfate-induced irritant contact dermatitis on in vivo percutaneous penetration was investigated for four 14C-labeled compounds with diverse physicochemical properties: hydrocortisone (HC), indomethacin (IM), ibuprofen (IB), and acitretin (AC). Hairless guinea pigs were pretreated for 24 h with either 0.5% sodium lauryl sulfate (SLS) to induce irritant contact dermatitis or with water (controls). Twenty-four hours after pretreatment, 450 microliters saturated solutions of HC, IM, IB, or AC in isopropylmyristate were applied to the pretreated skin for 24 h. Systemic absorption was determined by urinary and fecal excretion of compounds. Drug concentrations in stratum corneum (obtained by tape cellophane stripping after decontamination of the application site) and in epidermis/dermis (punch biopsy) were also investigated. Systemic absorption of topically applied drugs (as evaluated by urinary and fecal excretion) in SLS-irritated skin was significantly increased for HC (factor 2.6) followed by IB (1.9 times) and IM (1.6 times) but not increased for AC. However, drug concentrations in the viable epidermis and dermis were 70% lower in SLS-irritated than normal skin for HC, but not different for IB, IM, and AC. Thus, the influence of the state of the skin (irritant dermatitis versus healthy) on percutaneous penetration was different for diverse drugs. The general assumption that percutaneous penetration and drug tissue concentrations were higher in diseased versus healthy skin was not found to be true in our irritated-skin model.
研究了月桂醇硫酸酯钠诱导的刺激性接触性皮炎对四种具有不同理化性质的14C标记化合物体内经皮渗透的影响：氢化可的松（HC）、吲哚美辛（IM）、布洛芬（IB）和阿维A（AC）。将无毛豚鼠用0.5%月桂醇硫酸酯钠（SLS）预处理24小时以诱导刺激性接触性皮炎，或用水预处理（作为对照）。预处理24小时后，将450微升HC、IM、IB或AC在肉豆蔻酸异丙酯中的饱和溶液涂抹于预处理过的皮肤上24小时。通过化合物的尿液和粪便排泄来测定全身吸收情况。还研究了角质层（在去除涂抹部位污染物后通过胶带玻璃纸剥离获得）和表皮/真皮（打孔活检）中的药物浓度。对于HC，经皮局部给药药物的全身吸收（通过尿液和粪便排泄评估）在SLS刺激的皮肤中显著增加（系数为2.6），其次是IB（1.9倍）和IM（1.6倍），但AC没有增加。然而，对于HC，SLS刺激的皮肤中活表皮和真皮中的药物浓度比正常皮肤低70%，但对于IB、IM和AC则没有差异。因此，皮肤状态（刺激性皮炎与健康状态）对经皮渗透的影响因不同药物而异。在我们的皮肤刺激模型中，未发现患病皮肤与健康皮肤相比经皮渗透和药物组织浓度更高这一普遍假设成立。
