Structure-permeability relationship analysis of the permeation barrier properties of the stratum corneum and viable epidermis/dermis of rat skin.
The purpose of this study was to evaluate structure-permeability relationships for chemicals through stratum corneum (SC) and viable epidermis/dermis (VED). In vitro skin permeation of ten compounds through excised rat skin was analyzed based on a two-layer diffusion model and the diffusion coefficients in SC (D(SC)) and VED (D(VED)) were determined. The relationships between the permeation parameters and the physicochemical parameters (octanol-water partition coefficient (log K(o/w)), and hydrogen bond donor number (HBD)) of the compounds were analyzed. D(SC) increased as lipophilicity increased, whereas D(VED) decreased for log K(o/w) > 2. Increases in log K(o/w) caused a decrease in the permeability coefficient from SC through VED (P(VED/SC)) for log K(o/w) > 1. The simulation study suggests that the in vitro skin permeation of a highly lipophilic compound is strongly controlled by skin thickness due to low diffusivity in VED. The present study suggests that VED act as a considerable permeation barrier for highly lipophilic compounds due to low diffusivity.
Yamaguchi
Koji
K
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. yamaguchikuj@chugai-pharm.co.jp
Mitsui
Tetsuya
T
Aso
Yoshinori
Y
Sugibayashi
Kenji
K
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D004817:Epidermis / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D010539:Permeability; D010599:Pharmacokinetics; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D053719:Tandem Mass Spectrometry