Abstract
The effect of co-administration of vasoactive drugs on the transdermal iontophoretic delivery of lidocaine · HCI was studied in in vitro cells, in the isolated perfused porcine skin flap (IPPSF), and in vivo in pigs. Iontophoresis of lidocaine in vitro across human and porcine skin were similar, supporting the use of porcine skin as an appropriate animal model. Co-iontophoresis of the vasodilator tolazoline marginally decreased lidocaine flux in vitro, but significantly increased it in the IPPSF and in vivo. In contrast, norepinephrine decreased lidocaine flux in the IPPSF. Vasomodulation also changed the shape of the venous efflux profile in the IPPSF as evidenced by changes in fractional absorption index, as well as the AUC. These studies demonstrate that co-iontophoresis of vasoactive compounds may significantly alter the transdermal delivery of lidocaine and that use of in vitro animal model systems which possess a functional microcirculation are essential to study this process if reliable extrapolation to the in vivo setting is desired.
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