title: Usefulness of rat skin as a substitute for human skin in the in vitro skin permeation study.
abstract: Sprague-Dawley (SD) rats are broadly used in preclinical studies for drug development, so a lot of information for the rats can be obtained especially from pharmacokinetic, pharmacological and toxicological studies. The purpose of this study was to clarify whether SD rat skin can be used to predict human skin permeability. In vitro permeation studies of the three model drugs, nicorandil, isosorbide dinitrate, and flurbiprofen, through human skin and SD rat skin were performed using Franz-type diffusion cells. The permeation rates of the three model drugs through human skin and SD rat skin were determined, and their variations were evaluated. The inter-individual variations in SD rat skin permeability of the three model drugs were much lower than that in human skin permeability, although the permeation rates of the three model drugs through the SD rat skin were about twice those through human skin. In addition, no difference in the skin permeability coefficients of the three model drugs was obtained between fresh SD rat skin and frozen SD rat skin. The markedly smaller variation in the permeability through SD rat skin compared with that through human skin indicated that in vitro permeation studies using SD rat skin would be especially useful for evaluating differences in the skin permeability of the three model drugs as well as for predicting human skin permeability.
authors.affiliation: Pharmacokinetics and Metabolism, Drug Safety and Pharmacokinetics Laboratories, Pharmaceutical Business, Taisho Pharmaceutical Co., Ltd., 1–403 Yoshino, Kita-ku, Saitama 331-9530, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mano
authors.forename: Shuichi
authors.initials: S
authors.lastname: Terasaka
authors.forename: Takanobu
authors.initials: T
authors.lastname: Sakurai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Furuya
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Urano
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugibayashi
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000700:Analgesics / Q000493:pharmacokinetics*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004058:Diffusion; D005260:Female; D005480:Flurbiprofen / Q000493:pharmacokinetics; D006801:Humans; D007548:Isosorbide Dinitrate / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D023421:Models, Animal; D020108:Nicorandil / Q000493:pharmacokinetics; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D053719:Tandem Mass Spectrometry; D014665:Vasodilator Agents / Q000493:pharmacokinetics*
chemical_list: D000700:Analgesics; D014665:Vasodilator Agents; D020108:Nicorandil; D005480:Flurbiprofen; D007548:Isosorbide Dinitrate