Tojo K, Yamada K, Hikima T
Department of Biochemical Science and Engineering, College of Computer Science and Systems Engineering, Kyushu Institute of Technology, Fukuoka, Japan.
Pharm Res. 1994 Mar;11(3):393-7. doi: 10.1023/a:1018960920313.
The diffusion and metabolism of prednisolone 21-farnesylate were investigated in viable skin of the hairless mouse in vitro. The prodrug ester was extensively metabolized in viable skin, while it was stable in the donor and receptor solutions. The rate of appearance of the prodrug and its metabolite prednisolone was markedly influenced by the direction of the skin placed between the in vitro diffusion half-cells. The rate of bioconversion of the prodrug was determined as a function of the distance from the surface of the skin. The prodrug was increasingly metabolized with the distance from the surface of the skin, indicating that the responsible enzymes are enriched in the lower layers of the viable skin. A model with linearly increasing enzyme activity in the viable skin accounts for the in vitro profiles of the diffusion/metabolism of the prodrug in the viable skin of hairless mouse.
对21-法呢基泼尼松龙在无毛小鼠活体皮肤中的扩散和代谢进行了体外研究。前体药物酯在活体皮肤中被广泛代谢，而在供体溶液和受体溶液中则很稳定。前体药物及其代谢产物泼尼松龙的出现速率受到置于体外扩散半透膜之间皮肤方向的显著影响。前体药物的生物转化速率被确定为距皮肤表面距离的函数。前体药物随着距皮肤表面距离的增加而代谢得越来越多，这表明相关酶在活体皮肤的下层富集。一个在活体皮肤中酶活性呈线性增加的模型解释了前体药物在无毛小鼠活体皮肤中扩散/代谢的体外特征。
