Limitation of Potts and Guy's model and a predictive algorithm for skin permeability including the effects of hydrogen-bond on diffusivity.
The Potts and Guy's model for skin permeability, log P = alpha log K - beta MV + delta where P is the permeability coefficient of a compound from aqueous solution through human skin in vitro, K and MV are octanol-water partition coefficient and molecular volume of the compound respectively, and alpha, beta, delta are constants, is examined for a data set of 53 miscellaneous compounds. The model will result in over-estimation for penetrants having higher hydrogen-bond donor activity and underestimation for penetrants having no hydrogen-bond donor. A predictive algorithm for skin permeability including the effects of hydrogen-bond on diffusivity is proposed: log P = alpha log K - beta MV - gamma Hb + delta where Hb is the descriptor of hydrogen-bonding capacity of penetrants and gamma is a constant. The calculated log P values from the latter model are in good accordance with respective experimental ones for the data set.
Fu
X C
XC
Department of Pharmacy, Zhejiang University City College, Hangzhou, PR China. Fuxc@zucc.edu.cn
Wang
G P
GP
Wang
Y F
YF
Liang
W Q
WQ
Yu
Q S
QS
Chow
M S S
MS
D000465:Algorithms; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004058:Diffusion; D006801:Humans; D006860:Hydrogen Bonding; D008954:Models, Biological; D000442:Octanols / Q000737:chemistry; D010539:Permeability; D011237:Predictive Value of Tests; D012869:Skin Absorption; D012995:Solubility; D014867:Water / Q000737:chemistry
D000442:Octanols; D014867:Water