Shah V P, Epstein W L, Riegelman S
J Clin Invest. 1974 Jun;53(6):1673-8. doi: 10.1172/JCI107718.
Griseofulvin, an orally effective antimicrobial agent, appears in the stratum corneum within 4-8 h after oral administration. Griseofulvin distribution was found to be highest in the outermost layers of the stratum corneum (level I, 20.8+/-1.5 ng/mg) and lowest inside (level II, 10.0+/-1.5; level III, 7.5+/-2.2 ng/mg). In order to study the precise mechanism of griseofulvin transfer to stratum corneum, the role of sweat in the accumulation of griseofulvin was considered. Heat-induced total body sweating decreased the mean stratum corneum concentration of griseofulvin by 55%, and 200-300 ng of griseofulvin accumulated per ml of sweat. A silicone hydrophobic resin was used to differentiate between "wash-off" and carrier properties of sweat for griseofulvin. Prevention of transepidermal water and sweat loss by (a) topical application of formaldehyde-releasing cream to one palm, (b) occlusion by a 2 x 2-cm patch on one arm, and (c) wearing a rubber glove for 24 h, showed a lower griseofulvin concentration when compared to control areas in the same subjects. The results of the gloved hand experiment show that a complete equilibrium is established at all three levels of stratum corneum, thereby removing the reversed gradient. These results support the hypothesis that a "wick effect" is responsible for the observed reversed drug gradient within the stratum corneum. The results of the experiments suggest that sweat and transepidermal fluid loss play an important role in griseofulvin transfer in stratum corneum.
灰黄霉素是一种口服有效的抗菌剂，口服给药后4 - 8小时出现在角质层中。研究发现，灰黄霉素在角质层最外层的分布最高（I层，20.8±1.5 ng/mg），在内部最低（II层，10.0±1.5；III层，7.5±2.2 ng/mg）。为了研究灰黄霉素转运至角质层的精确机制，考虑了汗液在灰黄霉素蓄积中的作用。热诱导的全身出汗使角质层中灰黄霉素的平均浓度降低了55%，每毫升汗液中蓄积200 - 300 ng灰黄霉素。使用硅酮疏水树脂来区分汗液对灰黄霉素的“冲洗”和载体特性。通过以下方式预防经表皮水分和汗液流失：(a) 在一只手掌局部应用释放甲醛的乳膏，(b) 在一只手臂上用2×2 cm的贴片封闭，(c) 戴橡胶手套24小时，与同一受试者的对照区域相比，灰黄霉素浓度较低。戴手套手部实验的结果表明，在角质层的所有三个层面都建立了完全平衡，从而消除了反向梯度。这些结果支持了一种假设，即“芯吸效应”是角质层内观察到的药物反向梯度的原因。实验结果表明，汗液和经表皮液体流失在角质层中灰黄霉素的转运中起重要作用。
