title: Model describing transdermal iontophoretic delivery of lidocaine incorporating consideration of cutaneous microvascular state.
abstract: 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.
authors.affiliation: Cutaneous Pharmacology and Toxicology Center, North Carolina State University, Raleigh 27606.
authors.forename: P L
authors.initials: PL
authors.lastname: Williams
authors.forename: J E
authors.initials: JE
authors.lastname: Riviere
mesh_terms: 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
chemical_list: D008012:Lidocaine; D014043:Tolazoline; D009638:Norepinephrine