Ritschel W A, Hussain A S
Division of Pharmaceutics, University of Cincinnati Medical Center, OH.
Arzneimittelforschung. 1988 Nov;38(11):1630-2.
Penetration and permeation of griseofulvin into and across the rat skin after application of three ointment formulations containing either dimethylacetamide (DMAC) or diethylene glycol monoethylether (DGME) or the ointment base alone (control--without DMAC or DGME) were studied, in vitro. Penetration and permeation of griseofulvin into and across the human skin after application of DGME ointment was also studied. Permeation of griseofulvin across the rat skin was highest for the DMAC ointment, followed by the DGME ointment and lowest for the control. Concentration of griseofulvin in the upper layers of the skin (i.e., surface to 100 micron depth) was also highest for DMAC and lowest for the control. However, the skin levels from the DGME ointment could not be distinguished (statistically) from the other two formulations. In comparison to rat skin, human skin is much less permeable. Amount of griseofulvin (from DGME ointment) that permeated through the rat skin was 14 times the amount that permeated through the human skin. Concentration of griseofulvin in the upper layers of the rat skin were 4 times the concentration of the drug in the upper layers of the human skin. The concentration of griseofulvin in the various layers of the human skin after one topical application were far greater than those reported after prolonged peroral administration.
体外研究了三种分别含有二甲基乙酰胺（DMAC）或二甘醇单乙醚（DGME）的软膏制剂或仅含软膏基质（对照——不含DMAC或DGME）应用后，灰黄霉素渗透进入和穿过大鼠皮肤的情况。还研究了应用DGME软膏后，灰黄霉素渗透进入和穿过人体皮肤的情况。灰黄霉素穿过大鼠皮肤的渗透率以DMAC软膏最高，其次是DGME软膏，对照最低。皮肤上层（即表面至100微米深度）的灰黄霉素浓度也是DMAC最高，对照最低。然而，DGME软膏的皮肤药物含量在统计学上与其他两种制剂无法区分。与大鼠皮肤相比，人体皮肤的渗透性要低得多。（来自DGME软膏的）灰黄霉素透过大鼠皮肤的量是透过人体皮肤量的14倍。大鼠皮肤上层的灰黄霉素浓度是人体皮肤上层药物浓度的4倍。单次局部应用后，人体皮肤各层中的灰黄霉素浓度远高于长期口服给药后报道的浓度。
