TRANSPORT OF THE NEUTRAL FORM OF AMPHIPHILIC DRUGS THROUGH A PLANAR BILAYER LIPID-MEMBRANE - THE ROLE OF THE PH GRADIENT

The inner field compensation (IFC) method was used to measure the dependence of the boundary potential (BP) difference of a bilayer lipid membrane (BLM) on remantadin concentration. It was found that the BP difference depended on the pH gradient and the buffer capacity of the solution. The addition of remantadin at one side of the membrane caused changes in the pH values in the unstirred layers near both surfaces of the membrane. These changes were detected by means of measurement of the transmembrane open circuit potential in the presence of the protonophore pentachlorphenol. The sign of the transmembrane potential corresponded to a pH decrease on the membrane cis-side (where REM was added) and a rise on the irons-side. There was no increase in the membrane conductance due to the remantadin addition. A model of remantadin penetration through the lipid membrane is proposed. According to this model, the neutral form of the drug passes through the membrane. The formation and decomposition reactions of the neutral form, taking place at the membrane boundaries, are accompanied by the ejection and sorption of protons, respectively. The pH changes in lyzosomes or receptosomes due to remantadin penetration are discussed within the framework of the resulting model. © 1990.