QSAR analysis of skin permeability of various drugs in man as compared to in vivo and in vitro studies in rodents.
A general mathematical model involving partition coefficient, molecular weight and hydrogen bonding has been formulated for correlating the structures and skin permeability of a wide range of compounds through human skin and through hairless mouse skin. The correlations obtained are dependent not only on the biological system but also on the vehicle used. Without the use of lipophilic vehicle, the ideal lipophilicity for maximum permeability through human skin as measured by log Po(oct/w) ranges from 2.5 to 6 (extrapolated value). When a lipophilic vehicle was used in hairless mouse skin study, the log Po(oct/w) was lowered to around 0.4 approximately 0.6. While increased M.W. always has a negative effect on the permeability, increased H-bond can have either a slight positive or a slight negative effect, depending on the experiments (absorption vs. permeability constant). Cross validations with previously unanalyzed data as well as other biological systems support the usefulness of the general model developed for passive diffusion.
Lien
E J
EJ
University of Southern California School of Pharmacy, Department of Pharmaceutical Sciences, Los Angeles 90033, USA.
Gao
H
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D051379:Mice; D008812:Mice, Hairless; D010539:Permeability; D051381:Rats; D012869:Skin Absorption; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal