EPIDERMAL IONTOPHORESIS - II - APPLICATION OF THE IONIC MOBILITY-POREMODEL TO THE TRANSPORT OF LOCAL-ANESTHETICS

Purpose, An in vitro study was carried out to determine the iontophore tic permeability of local anesthetics through human epidermis. The rel ationship between physicochemical structure and the permeability of th ese solutes was then examined using an ionic mobility-pore model devel oped to define quantitative relationships. Methods. The iontophoretic permeability of both ester-type anesthetics (procaine, butacaine, tetr acaine) and amide-type anesthetics (prilocaine, mepivacaine, lidocaine , bupivacaine, etidocaine, cinchocaine) were determined through excise d human epidermis over 2 hrs using a constant d.c. current and Ag/AgCl electrodes. Individual ion mobilities were determined from conductivi ty measurements in aqueous solutions. Multiple stepwise regression was applied to interrelate the iontophoretic permeability of the solutes with their physical properties to examine the appropriateness of the i onic mobility-pore model and to determine the best predictor of iontop horetic permeability of the local anesthetics. Results. The logarithm of the iontophoretic permeability coefficient (log PCj,iont) for local anesthetics was directly related to the log ionic mobility and MW for the free volume form of the model when other conditions are held cons tant. Multiple linear regressions confirmed that log PCj,iont was best defined by ionic mobility (and its determinants: conductivity, pK(a) and MW) and MW. Conclusions. Our results suggest that of the propertie s studied, the best predictors of iontophoretic transport of local ane sthetics are ionic mobility (or pK(a)) and molecular size. These predi ctions are consistent with the ionic mobility pore model determined by the mobility of ions in the aqueous solution, the total current, epid ermal permselectivity and other factors as defined by the model.