Corneal Penetration Behavior of β-Blocking Agents III: In Vitro–In Vivo Correlations

Abstract

Aqueous humor levels were determined over time after the topical administration to rabbit eyes of 1% isotonic buffered (pH7.3) solutions of three β-blocking agents, acebutolol hydrochloride, timolol maleate, and bufuralol hydrochloride (arranged in order of increasing lipophilicity). Corneal permeability coefficients, determined from a previous in vitro study, were inversely related to the observed time to peak for the three drugs, as expected. Two of the drugs, bufuralol and timolol, did not give the expected rank order for Cmax and AUC, which could result from differences in distribution and/or elimination processes. Aqueous boundary layers were postulated for in vivo comeal permeability which suggested that bufuralol and timolol may have nearly identical effective permeability coefficients in vivo.