Evaluation of the membrane permeability of drugs by ion-transfer voltammetry with the oil | water interface

Abstract

Ion transfer voltammetry with the polarized 1,2-dichloroethane (DCE)|water (W) interface was carried out to determine the standard ion-transfer potential (∆OWϕ∘) and the distribution coefficient (logKD) for amine drugs, including desipramine, imipramine, labetalol, etc. The values of ∆OWϕ∘ and logKD are the hydrophobicity scales for the ionized and neutral forms of a drug, respectively, and were found to show a good mutual correlation. However, these hydrophobicity scales did not show a good correlation to the 1-octanol–water partition coefficient (logPoct) being conventionally used. In contrast, the permeability coefficient (logPpampa) in the parallel artificial membrane permeation assay showed a clear and characteristic dependence on ∆OWϕ∘ (or logKD). These results suggested that the solvation environment in DCE should be more similar to that in the hydrocarbon region of lipid bilayers than in 1-octanol. Thus, it was shown that ∆OWϕ∘, which can be easily determined by ion-transfer voltammetry, is a promising scale for predicting drug permeability through lipid membranes.