Model describing transdermal iontophoretic delivery of lidocaine incorporating consideration of cutaneous microvascular state.

A three-compartment pharmacokinetic model describing percutaneous absorption of iontophoretically driven topically applied lidocaine in the isolated perfused porcine skin flap is presented. Delivery from the active (drug-dosed) electrode to skin is estimated as a ramp input profile. Model parameters were estimated separately for dosing (4 h current-on) and washout (4 h current-off) periods in experiments with coadministered vasoactive drugs [tolazoline (vasodilator) and norepinephrine (vasoconstrictor)] and controls (lidocaine alone). The model presented was able to predict 8-h lidocaine absorptions and compartmental mass profiles for each of the three treatments, was able to document vascular effects of co-iontophoresed vasoactive compounds, and gives insight into the factors that modulate cutaneous disposition of iontophoretically delivered lidocaine in a biologically relevant model approximating in vivo delivery.