Unified Model for the Corneal Permeability of Related and Diverse Compounds with Respect to Their Physicochemical Properties

• Published in: Journal of pharmaceutical sciences 1996-08, Vol.85 (8), p.819-823
• Main Authors: Yoshida, Fumitaka, Topliss, John G.
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - pharmacokinetics; Biological and medical sciences; Cornea - metabolism; General pharmacology; Medical sciences; Models, Biological; Permeability; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Steroids - pharmacokinetics
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1021/js960076m

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 β-adrenoceptor blockers and steroids, the correlation was reduced when taken together. However, Δ log P (i.e., log Poctanol−log Palkane) correlated inversely with the combined permeability data for β-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 Δ 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 Δ log P and lipophilicity.