title: Unified model for the corneal permeability of related and diverse compounds with respect to their physicochemical properties.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor 48109-1065, USA.
authors.forename: F
authors.initials: F
authors.lastname: Yoshida
authors.forename: J G
authors.initials: JG
authors.lastname: Topliss
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D003315:Cornea / Q000378:metabolism*; D008954:Models, Biological; D010539:Permeability; D013256:Steroids / Q000493:pharmacokinetics*
chemical_list: D000319:Adrenergic beta-Antagonists; D013256:Steroids