Utility of hairless rats as a model for predicting transdermal pharmacokinetics in humans

Abstract

1. This study investigated the use of HWY hairless rats to predict human plasma concentrations of drugs following dermal application.

2. Utilizing a deconvolution method, pharmacokinetic parameters (e.g. in vivo absorption rates) were determined for six transdermal drugs in hairless rats. Obtained data were used to simulate the human plasma concentration-time profiles of transdermal drugs, which were then compared with clinical data in humans. Because hairless rats have lower hair follicle density than do humans, the impact of hair follicle density on skin permeability to hydrophilic compounds was also evaluated.

3. Pharmacokinetic parameters showed low intra-individual variability in hairless rats. Simulated concentration profiles for compounds with logarithm of the octanol–water partition coefficient exceeding two were comparable to clinical data, but simulated concentration profiles for hydrophilic compounds (i.e. bisoprolol and nicotine) at maximum concentration differed from clinical data by more than two-fold. Finally, in vitro permeability to bisoprolol and nicotine was higher in human skin than in hairless rat skin, but hair follicle plugging reduced human skin permeability.

4. In vivo skin absorption data from HWY hairless rats help to predict human concentration profiles for lipophilic compounds. However, the data underestimate human absorption of hydrophilic compounds.

Keywords:

• In vitro–in vivo correlations (IVIVC)
• hairless rat
• skin absorption
• skin permeability
• transdermal

Acknowledgments

We would like to thank all of our colleagues for their comments, insights and helpful discussions.

Disclosure statement

No potential conflict of interest was reported by the authors.