Percutaneous penetration of drugs: a quantitative structure-permeability relationship study.
Human skin permeation data taken from the literature were analyzed for quantitative relationships with physicochemical properties and structural descriptors. No correlations exist with molecular weights and solvent-accessible surface areas. In most cases, skin permeation was inversely correlated with the parameter delta log Poct-hep (i.e., log Poctanol minus log Pheptane), which is mainly a measure of the H-bond donor acidity of the solutes. Lipophilicity itself, as expressed by log Poctanol, also contributes positively to skin permeation in some cases. The results of this quantitative structure-permeability relationship study are interpreted in terms of a unified mechanistic model whereby drugs can permeate via an intercellular route (correlation with both delta log Poct-hep and log Poct) and/or a transcellular route (correlation with log Poct only).
el Tayar
N
N
School of Pharmacy, University of Lausanne, Switzerland.
Tsai
R S
RS
Testa
B
B
Carrupt
P A
PA
Hansch
C
C
Leo
A
A
D000287:Administration, Topical; D000438:Alcohols / Q000737:chemistry / Q000493:pharmacokinetics; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D006854:Hydrocortisone; D006860:Hydrogen Bonding; D008970:Molecular Weight; D000442:Octanols; D010636:Phenols / Q000737:chemistry; D012869:Skin Absorption; D012995:Solubility; D012997:Solvents; D013256:Steroids / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship; D013499:Surface Properties
D000438:Alcohols; D000893:Anti-Inflammatory Agents; D000442:Octanols; D010636:Phenols; D012997:Solvents; D013256:Steroids; D006854:Hydrocortisone