Sugibayashi Kenji, Hayashi Teruaki, Matsumoto Kaori, Hasegawa Tetsuya
Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.
Drug Metab Pharmacokinet. 2004 Oct;19(5):352-62. doi: 10.2133/dmpk.19.352.
The simultaneous diffusion and metabolism of ethyl nicotinate (EN) in a cultured human skin model, Living Skin Equivalent-high, was evaluated by the in vitro skin permeation and metabolism experiments, and esterase distribution was also determined. Theoretical calculations using Fick's 2nd Law of Diffusion with Michaelis-Menten kinetics were performed to obtain the permeation and metabolic parameters together with information on enzyme distribution. The obtained data was compared with the corresponding results in excised hairless rat skin. The partition coefficient of EN from the vehicle to the skin was of the same order of magnitude for the cultured human skin and hairless rat skin, but the diffusion and metabolic parameters were different. Esterase concentration in the epidermal membrane was greater than in the dermis of cultured skin, which was similar to hairless rat skin. Taking into account the similarities and differences between the membranes, the cultured human skin model can be utilized as a model membrane to rapidly predict simultaneous diffusion and metabolism of the prodrug through human skin.
通过体外皮肤渗透和代谢实验，评估了烟酸乙酯（EN）在一种培养的人类皮肤模型——高级活皮肤等效物中的同时扩散和代谢情况，并测定了酯酶分布。使用菲克第二扩散定律结合米氏动力学进行理论计算，以获得渗透和代谢参数以及酶分布信息。将所得数据与切除的无毛大鼠皮肤中的相应结果进行比较。EN从载体到皮肤的分配系数在培养的人类皮肤和无毛大鼠皮肤中处于同一数量级，但扩散和代谢参数不同。培养皮肤的表皮膜中的酯酶浓度高于真皮中的酯酶浓度，这与无毛大鼠皮肤相似。考虑到这些膜之间的异同，培养的人类皮肤模型可作为一种模型膜，用于快速预测前体药物通过人类皮肤的同时扩散和代谢。
