Unified model for the corneal permeability of related and diverse compounds with respect to their physicochemical properties

J Pharm Sci. 1996 Aug;85(8):819-23. doi: 10.1021/js960076m.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacokinetics*
  • Cornea / metabolism*
  • Models, Biological
  • Permeability
  • Steroids / pharmacokinetics*

Substances

  • Adrenergic beta-Antagonists
  • Steroids