Quantitative prediction of transdermal iontophoretic delivery of arbutamine in humans with the in vitro isolated perfused porcine skin flap.
The use of the isolated perfused porcine skin flap (IPPSF), an alternative in vitro animal model, to predict the profile of the concentration of arbutamine in plasma samples from humans after transdermal iontophoretic administration of this novel catecholamine is described. The strategy involved administering the drug in the IPPSF (n = 8) and assaying concentrations of drug in the venous efflux versus time (IPPSF venous efflux profile). Intravenous infusion (n = 7) and transdermal studies (n = 32) were also conducted in humans. The IPPSF profile was then used as an input into an intravenous pharmacokinetic model obtained from the human experiments to predict the profile of concentration of drug in plasma versus time (plasma concentration-time profile) seen after iontophoretic administration. The IPPSF profiles were denormalized according to the parameters used in the human studies (i.e., multiplied by in vivo concentration, electrode area, current, and dosing time). For two different sets of iontophoretic dosing conditions, the concentration-time profiles that were predicted on the basis of the IPPSF study were compared with those seen after delivery to humans.
Riviere
J E
JE
Cutaneous Pharmacology and Toxicology Center, North Carolina State University, Raleigh 27606.
Williams
P L
PL
Hillman
R S
RS
Mishky
L M
LM
D000279:Administration, Cutaneous; D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002395:Catecholamines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004566:Electrodes; D006801:Humans; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D007478:Iontophoresis; D008297:Male; D013552:Swine
D002316:Cardiotonic Agents; D002395:Catecholamines; C076559:arbutamine