Abstract
The purpose of this study was to investigate the effect of vasoactive drugs on transdermal lidocaine inotophoresis by measuring the concentrations of radiolabeled lidocaine which has penetrated the skin. Previous studies had demonstrated that coinotophoresis of vasoactive drugs could modulate the transcutaneous flux of lidocaine and suggested that a dermal depot of lidocaine was involved. To address this, lidocaine hydrochloride (14C) was iontophoresed in vivo in anesthetized weanling pigs either alone or with the vasodilator tolazoline or the vasoconstrictor norepinephrine. Tissue cores under the active electrode were then collected, quick-frozen, and sectioned on a cryostat, and then the radioactivity was determined in each 40-microns section. Coiontophoresis with norepinephrine resulted in increased concentrations of lidocaine in skin up to a depth of 3 mm. These concentrations decreased to lidocaine-alone levels after a 4-hr washout. Tolazoline decreased tissue concentrations of lidocaine. Concentrations were intermediate when lidocaine alone was administered. These studies support the hypothesis that coiontophoresis of vasoactive drugs modulates the transdermal delivery of lidocaine, in part by altering the cutaneous "depot."
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