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 Jun;96(6):963-7. doi: 10.1111/1523-1747.ep12476269.
The influence of irritant contact dermatitis on 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 in vivo 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 animals were sacrificed. Percutaneous penetration was then measured using in vitro diffusion cells and the removed (pretreated) skin. The following parameters were determined: cumulative amount of compound penetrated, steady state flux, lag time, and permeability coefficient, skin concentration per unit area, and the relative amount of drug remaining in the skin (as a percentage of the cumulative amount of compound penetrated through the skin). SLS pretreatment resulted in moderate irritant dermatitis in all animals and increased in vivo transepidermal water loss 4.5 times. Flux was increased in SLS-pretreated skin as compared with controls for all four compounds, with the greatest enhancement for hydrocortisone (HC) (5.9 times), followed by indomethacin (IM) (4.6 times), ibuprofen (IB) (3.9 times), and acitretin (AC) (3.4 times). Skin concentrations increased to a smaller degree from 1.6 times (IB) and 2.6 times (HC) to 3.4 times (IM). However, AC skin concentrations were not different between the two groups. Thus, percutaneous penetration parameters were equivocally influenced by SLS-induced irritation. Increased skin concentrations were paralleled by even higher increases in flux.
研究了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）。将无毛豚鼠在体内分别用0.5%十二烷基硫酸钠（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小时后处死动物。然后使用体外扩散池和去除的（预处理过的）皮肤测量经皮渗透。测定了以下参数：化合物渗透的累积量、稳态通量、滞后时间和渗透系数、单位面积皮肤浓度以及皮肤中残留药物的相对量（占经皮肤渗透的化合物累积量的百分比）。SLS预处理导致所有动物出现中度刺激性皮炎，并使体内经表皮水分流失增加4.5倍。与对照组相比，所有四种化合物在SLS预处理的皮肤中的通量均增加，氢化可的松（HC）增加幅度最大（5.9倍），其次是吲哚美辛（IM）（4.6倍）、布洛芬（IB）（3.9倍）和阿维A（AC）（3.4倍）。皮肤浓度升高程度较小——从布洛芬（IB）的1.6倍和氢化可的松（HC）的2.6倍到吲哚美辛（IM）的3.4倍。然而，两组之间阿维A（AC）的皮肤浓度没有差异。因此，SLS诱导的刺激对经皮渗透参数的影响不明确。通量的更高增加与皮肤浓度的增加并行。
