The effect of saline iontophoresis on skin integrity in human volunteers. I. Methodology and reproducibility.

This study, conducted in 36 human volunteers, was an evaluation of the effects of saline iontophoresis on skin temperature, irritation, and barrier function. The major objectives were to assess the effects of low-level ionic currents, to validate the proposed methodology of assessment, and to establish reproducibility in repeated saline iontophoresis applications. This was the first of a multistage study designed to assess the safety of 24-hr saline iontophoresis episodes at selected currents and current densities. Since an iontophoresis patch challenges the skin barrier both by occluding the skin surface and by passing ionic current through the skin, the experimental protocol was designed to permit measurement of the contribution of each of these processes to the overall response. In this first stage we investigated the effect of 10 min of current delivery, at 0.1 mA/cm2 on a 1-cm2 area patch and 0.2 mA/cm2 on a 6.5-cm2 area patch compared to unpowered control patches. Twelve subjects were tested under each condition on two separate occasions to examine reproducibility of the response variable measurements. A further 12 subjects were tested once under the 0.2 mA/cm2, 6.5-cm2 condition. Skin irritation was evaluated via repeated measurements of transepidermal water loss, capacitance, skin temperature, skin color, and a visual scoring system, before the iontophoresis episode and after patch removal. No damage to skin barrier function in terms of skin-water loss or skin-water content was detected. Slight, subclinical, short-lasting erythema was observed for both conditions. Assessment of correlation coefficients showed highly statistically significant indications of reproducibility for all five response variables measured. The experimental design, in combination with a repeated measures analysis, provided clear separation of the occlusion and ionic current components of the iontophoretic patch challenge. Further, the repeated measures analysis gave a highly sensitive assessment of skin irritation and resolution after patch removal. We conclude that the experimental methodology is appropriate for assessing possible changes in skin integrity resulting from saline iontophoresis under similar operating conditions for longer durations and for other skin challenges from which a subclinical response is expected.