In vitro and in vivo transdermal iontophoretic delivery of naloxone, an opioid antagonist

Aim: The feasibility of transdermal delivery of naloxone, an opioid antagonist, by anodal iontophoresis patches using Ag/AgCl electrodes was investigated. Methods: To examine the effect of current strength, species variation and drug concentration on skin permeability of naloxone, in vitro skin permeation studies were performed using rat dorsal skin and porcine ear skin as the membrane. To determine in vivo transdermal absorption rate of naloxone, the iontophoretic patch system was applied to the dorsal skin of conscious rat with a constant current supply for 24 h. Results: The in vitro steady-state skin permeation flux of naloxone current-proportionally (0-360 mu A/cm(2)) increased without significant differences between these two different skin types. The in vitro delivery rate through the porcine skin was found to be independent of the concentration of naloxone hydrochloride dehydrate in the donor patch over the range from 1 to 10% (w/v). In the in vivo pharmacokinetic study, plasma concentrations of naloxone steadily increased and sustained steady-state levels from 4 h to 24 h after the initiation of current application. In vivo steady-state transdermal absorption rates at 90 and 180 mu A/cm(2) were 136 and 305 mu g/h/cm(2), respectively. Conclusion: These results suggest that the transdermal delivery rates of naloxone by anodal iontophoresis are sufficient for the management of intoxication in opioid-overdosed patients. (C) 2011 Elsevier B.V. All rights reserved.