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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.

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Administration of ketamine before induction with propofol preserved haemodynamic stability compared with induction with propofol alone.

The purpose of this study was to clarify the influence of skin thickness on the in vitro permeabilities of 3 model drugs with different physicochemical properties (nicorandil (NR), isosorbide dinitrate (ISDN) and flurbiprofen (FP)) through Sprague-Dawley rat (rat) or Yucatan micropig (YMP) skin. Intact, dermis-split, stratum corneum-stripped or stratum corneum-stripped and dermis-split rat or YMP skin (rat skin thickness: approximately 0.4, 0.9 or 1.2 mm; YMP skin thickness: approximately 0.4, 0.9, 1.8 or 2.8 mm) were set in Franz-type diffusion cells to determine the permeation rate, lag time and resistance ratio of the viable epidermis and dermis against whole skin (R ved /R tot ) of the drugs. The YMP skin permeabilities of the drugs decreased with an increase in the skin thickness, and significant differences were observed in the permeation rates and lag times between intact and dermis-split (0.4 mm) YMP skins. The decreases in the permeabilities of the drugs through the YMP skin were larger than those through the rat skin. The influence of resistances of ISDN and FP through the dermis-split rat or YMP skin was greater at 0.9 mm skin thickness than 0.4 mm skin thickness. The R ved /R tot values for the YMP skins were relatively large for lipophilic drugs (ISDN and FP), and these ratios increased with an increase in the dermis thickness. These results suggest that in vitro skin permeation studies must be done using dermis-split (0.4 mm) skin with the thinnest dermis for predicting in vivo human percutaneous absorption rate.Key words Yucatan micropig; intact skin; stripped skin; split skin; skin permeabilityIn vitro skin permeation studies have been broadly used in the development of transdermal formulations. Animal skins are frequently used as an alternative to human skin in percutaneous absorption studies, because human skin is not always available and the use of human tissues and organs creates ethical problems.1-10) Numerous animal models, including primate, porcine, mouse, rat, guinea pig and pig, have been utilized for skin permeability studies. 1,3,4,[11][12][13] Animal skins with minimal variations in skin permeability may be much better than human skin for determining or estimating the skin permeabilities of drugs and for developing transdermal formulations. 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. 16,17) In addition, in vitro permeation studies using rat and YMP skin were particularly useful for evaluating differences in the skin permeabilities o...