title: Investigation of the mechanism of flux across human skin in vitro by quantitative structure-permeability relationships.
abstract: Permeability coefficients for 114 compounds across excised human skin in vitro were taken from Kirchner et al. Forty-seven descriptors were calculated encompassing the relevant physicochemical parameters of the compounds. Quantitative structure-permeability relationships (QSPRs) were developed using least-squares regression analysis. A two-parameter QSPR, describing the permeability coefficients (Kp) across excised skin, was obtained: log Kp=0.772 log P -0.0103 Mr - 2.33 where log P is the logarithm of the octanol-water partition coefficient and Mr is molecular mass. This equation indicates that percutaneous absorption is mediated by the hydrophobicity and the molecular size of the penetrant. Comparison with a QSPR based on penetration across a synthetic (polydimethylsiloxane) membrane suggests that the mechanisms of drug flux across polydimethylsiloxane membranes and excised human skin are significantly different.
authors.affiliation: School of Pharmacy and Chemistry, Liverpool John Moores University, Byrom Street, Liverpool L3 3AF, UK. m.t.cronin@livjm.ac.uk
authors.forename: M T
authors.initials: MT
authors.lastname: Cronin
authors.forename: J C
authors.initials: JC
authors.lastname: Dearden
authors.forename: G P
authors.initials: GP
authors.lastname: Moss
authors.forename: G
authors.initials: G
authors.lastname: Murray-Dickson
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006801:Humans; D006860:Hydrogen Bonding; D066298:In Vitro Techniques; D008970:Molecular Weight; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000502:physiology*; D013329:Structure-Activity Relationship