Importance of dermal blood supply and epidermis on the transdermal iontophoretic delivery of monovalent cations.

The effect of dermal blood flow on the transdermal iontophoresis of five monovalent cationic solutes has been investigated using an in vivo rat model. The iontophoretic flux of solutes from topical application sites was shown, using anesthetized and sacrificed rats, to be independent of the dermal blood supply. The presence of a viable blood supply significantly affected the extent of penetration of solutes into deeper underlying tissues during iontophoresis. Higher tissue concentrations of solutes were found in the upper tissue layers of sacrificed rats, with no blood supply, compared to those in anesthetized rats. In all animals the highest concentration of solute after 2 h iontophoresis was found in the epidermis. Iontophoretic application of solutes to skin with the epidermis removed resulted in significantly lower fluxes than from sites where the skin was intact. These findings suggest that local blood flow determines systemic and underlying tissue solute absorption but not epidermal penetration fluxes during iontophoretic delivery. Finally, the dependence of iontophoretic transport of a solute on the solute's size in vivo was similar to relationships previously reported for excised human skin studies.