Drug permeation through human skin II: Permeability of ionizable compounds.
Drug permeation through human skin II: Permeability of ionizable compounds.
复制标题
药物通过人体皮肤的渗透 II：可电离化合物的渗透性。
DOI：
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发表时间：
1984
期刊：
影响因子：
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通讯作者：
N. Gensmantel
中科院分区：
文献类型：
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作者：
J. Swarbrick;Geoffrey Lee;J. Brom;N. Gensmantel
本研究的目的是确定pKa值小于2的某些4-氧代-4H-1-苯并吡喃-2-羧酸（色酮-2-羧酸）的离子化和非离子化形式是否透过离体人皮肤，如果是，则确定渗透物质的渗透系数。用有机玻璃扩散池研究了四种羧酸在37 ℃下在pH 5 - 7范围内的渗透性能随浓度的变化。J/CA-（在稳态条件下，供体室中每单位浓度的离子化药物产生的非离子化和离子化物质的总通量）与CH3O+的曲线图呈直线关系。这些图的截距显示为等于PA-，而斜率乘以化合物的Ka值等于PHA，分别是电离和非电离物质的渗透系数。对于所有四种化合物，发现两种物质均渗透皮肤，尽管未电离物质的渗透系数比电离物质的渗透系数大约10（4）。据证明，离子化和非离子化物质对总通量的相对贡献以及总通量显著变化，这取决于供体池中药物溶液的pH值。这可以提供控制这些和类似化合物通过人体皮肤的通量的手段。
The aim of this study was to establish whether ionized as well as un-ionized forms of certain 4-oxo-4H-1-benzopyran-2-carboxylic acids (chromone-2-carboxylic acids) with pKa values less than 2 permeated through excised human skin and, if so, to determine the permeability coefficients of the permeating species. The permeation properties of four carboxylic acids were studied as a function of concentration over the pH range 5-7 at 37 degrees C with plexiglass diffusion cells. Plots of J/CA- (the total flux due to un-ionized and ionized species obtained under steady-state conditions per unit concentration of ionized drug in the donor compartment) against CH3O+ resulted in straight-line relationships. The intercepts of these plots were shown to equal PA-, whereas the slopes multiplied by the Ka values of the compounds equalled PHA, the permeability coefficients of the ionized and un-ionized species, respectively. With all four compounds, both species were found to permeate skin, although the permeability coefficients of the un-ionized species were approximately 10(4) greater than those for the ionized species. It was demonstrated that the relative contributions of the ionized and un-ionized species to the total flux, as well as the total flux, vary significantly, depending on the pH of the drug solution in the donor cell. This may provide a means of controlling the flux of these and similar compounds through human skin.