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.

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

“…Along with the pig skin model, employed due to its barrier properties comparable to human skin as well as a better availability (Herkenne et al, 2006), rat skin is also used for dermal penetration studies (Takeuchi et al, 2011). Rat skin is mainly employed in the plant protection area, for systemic toxicology studies and in vivo skin absorption studies.…”

Influence of Skin Thickness on the in Vitro Permeabilities of Drugs through Sprague-Dawley Rat or Yucatan Micropig Skin

“…1,14,15) In our previous studies, the in vitro permeation of 3 model drugs was investigated through Sprague-Dawley rat (rat), Yucatan micropig (YMP) and human skin. 16,17) The 3 model drugs were selected because of their different log K o/w values (the logarithm of the octanol/water partition coefficient at 37°C; Table 1). 18) Nicorandil (NR), isosorbide dinitrate (ISDN) and flurbiprofen (FP) were used as hydrophilic, lipophilic and highly lipophilic drugs, respectively. The inter-individual variations in rat and YMP skin permeabilities for the 3 drugs were smaller than the human skin permeability.…”

“…The inter-individual variations in rat and YMP skin permeabilities for the 3 drugs were smaller than the human skin permeability. 16,17) In addition, in vitro permeation studies using rat and YMP skin were particularly useful for evaluating differences in the skin permeabilities of the model drugs and for predicting human skin permeability. 16,17) Guidelines for a standard experimental protocol for in vitro skin permeation studies were published by the Organization Regular Article * To whom correspondence should be addressed.…”

“…Nevertheless, we attempted to dermatome the skin using an electric dermatome by a new method established in our previous studies. 16,17) The purpose of this study was to clarify the influence of skin thickness on the in vitro permeabilities of 3 drugs with different physicochemical properties through rat or YMP skin. To accurately determine the permeation rate of drugs through rat or YMP skin, in vitro permeation experiments were performed using split rat and YMP skin of various thicknesses.…”

Optimization and Formulation Development of Cefixime Complex Using Spray Drying Technique: DOE Approach

“…The positive as well as negative signs of the coefficient values in the equations acquired following statistical investigation correspond to the agonistic & antagonistic outcome of the self-determining variable whereas the degree of beta coefficient symbolizes the degree of effect of the analogous independent variables [29][30][31].…”