The aim of this study was to investigate whether transdermal delivery of domperidone can be enhanced to therapeutic levels by iontophoresis and/or electroporation. In vitro studies were performed with a solution of domperidone pH 3.5 in 9.5% (v/v) ethanol. Iontophoresis (2 h at 0.4 mA/cm(2)) increased the transdermal permeation by a factor 15 as compared to passive diffusion. Application of 5 long (tau = 700 ms) high-voltage (250 V) pulses increased the domperidone permeation by a factor of up to 70. Application of one pulse (250 V-700 ms) prior to iontophoresis provided similar penetration enhancement to 5 pulses (250 V-700 ms). No significant enhancement was provided by application of one short pulse (1000 V-4 ms) prior to iontophoresis, probably due to a different mechanism of permeabilization and/or recovery kinetics to the initial permeability state. The domperidone permeation flux by skin electroporation (1.5 mu g/cm(2) h) is in the range of the fluxes measured with chemical penetration enhancers but the lag time was reduced. However, due to the low hydrosolubility of domperidone, electrically enhanced flux remains too low for therapeutic application. (C) 1997 Elsevier Science B.V.