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 on...

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Bibliographic Details
Published in:Pharmaceutical research 1995-04, Vol.12 (4), p.583-587
Main Authors: LIEN, E. J, HUA GAO
Format: Article
Language:English
Subjects:
Animals
Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics
Biological and medical sciences
Female
General pharmacology
Humans
Medical sciences
Mice
Mice, Hairless
Permeability
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Rats
Skin Absorption
Structure-Activity Relationship
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Summary: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.
ISSN:0724-8741
1573-904X
DOI:10.1023/A:1016266316100