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.
Williams
P L
PL
Cutaneous Pharmacology and Toxicology Center, North Carolina State University, Raleigh 27606.
Riviere
J E
JE
D000279:Administration, Cutaneous; D000818:Animals; D007478:Iontophoresis; D008012:Lidocaine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008954:Models, Biological; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D012867:Skin / Q000098:blood supply*; D012869:Skin Absorption; D013552:Swine; D014043:Tolazoline / Q000494:pharmacology
D008012:Lidocaine; D014043:Tolazoline; D009638:Norepinephrine