Unified model for the corneal permeability of related and diverse compounds with respect to their physicochemical properties.
Corneal permeability data taken from the literature were analyzed for possible quantitative relationships with physicochemical properties. Although a parabolic relationship was obtained with good correlation between lipophilicity, as expressed by the 1-octanol-water partition coefficients, log Poctanol (or the distribution coefficients, log D for ionizable compounds), and the permeability in individual analyses of compound classes such as beta-adrenoceptor blockers and steroids, the correlation was reduced when taken together. However, delta log P (i.e., log Poctanol-log Palkane) correlated inversely with the combined permeability data for beta-blockers and steroids and played a key role as a unifying variable. To a lesser extent, lipophilicity itself also contributes positively to corneal permeation. Even with the addition of miscellaneous compounds such as methanol and ibuprofen, the delta log P and lipophilicity terms were still significant. However, small molecules were likely to be underestimated, which is consistent with penetration via another pathway besides that governed by delta log P and lipophilicity.
Yoshida
F
F
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.
Topliss
J G
JG
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D003315:Cornea / Q000378:metabolism*; D008954:Models, Biological; D010539:Permeability; D013256:Steroids / Q000493:pharmacokinetics*
D000319:Adrenergic beta-Antagonists; D013256:Steroids