NONINVASIVE ASSESSMENT OF SKIN BARRIER INTEGRITY AND SKIN IRRITATION FOLLOWING IONTOPHORETIC CURRENT APPLICATION IN HUMANS

Iontophoresis is believed to have great added value for the delivery o f drugs to the systemic circulation via the transdermal route. Whether iontophoretic transdermal systems can be applied for a wide variety o f drugs, will at the same time depend on the intrinsic safety of curre nt application to the skin. We investigated the effect of electric cur rent in vivo on human skin by measuring two different aspects of the i rritant response: (a) the effect on the stratum corneum barrier functi on by measuring transepidermal water loss (TEWL); (b) effects at the l evel of the dermal vascular bed by measuring the erythematous response with Laser Doppler Flowmetry (LDF). Nine volunteers entered the study . DC (direct constant current) profiles were applied to the volar fore arms of the subjects for 30 min. Following the application of DC and p ulsed DC current profiles, TEWL and LDF measurements were carried out on these sites, on so-called passive control sites (occluded by the ap plication chamber containing the buffer solution, but without applying current) and on untreated sites. TEWL values measured directly after patch removal were 1.5-2.0 times higher than the baseline values for T EWL regardless the presence or absence of electric current. The effect of the electric current application on the TEWL followed the same rel axation profile as the effect of buffer application without current. T he erythematous response however did differ significantly from the con trols. The response on the anodal sites was 1.5-2.7 times higher than at the cathodal sites. The erythema lasted from 25 to 69 min. The time span for relaxation of the erythema was independent of the current pr ofile (DC vs. pulsed DC) but was longer at the anodal sites than at th e cathodal sites. It was concluded from this study that after a single current application the effect on the barrier to water loss is neglig ible because the effect on TEWL cannot be distinguished from the occlu sive effect resulting from the application of the aqueous buffer alone , without current. The erythematous response to current application wa s relatively moderate and dependent on current direction.