title: In vitro and in vivo transdermal iontophoretic delivery of naloxone, an opioid antagonist.
abstract: OBJECTIVE
  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 24h.
  
  
  RESULTS
  The in vitro steady-state skin permeation flux of naloxone current-proportionally (0-360 μA/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 4h to 24h after the initiation of current application. In vivo steady-state transdermal absorption rates at 90 and 180 μA/cm(2) were 136 and 305 μg/h/cm(2), respectively.
  
  
  CONCLUSIONS
  These results suggest that the transdermal delivery rates of naloxone by anodal iontophoresis are sufficient for the management of intoxication in opioid-overdosed patients.
authors: Department of Device Development, TTI ellebeau, Inc., 4-8-8, Higashi-Shinagawa, Shinagawa-ku, Tokyo 140-0002, Japan.
authors: Rie
authors: R
authors: Yamamoto
authors: Shinri
authors: S
authors: Takasuga
authors: Yoshimasa
authors: Y
authors: Yoshida
authors: Shoichi
authors: S
authors: Mafune
authors: Katsuya
authors: K
authors: Kominami
authors: Chiyo
authors: C
authors: Sutoh
authors: Yukihiro
authors: Y
authors: Kato
authors: Mitsugu
authors: M
authors: Yamauchi
authors: Masao
authors: M
authors: Ito
authors: Kiyoshi
authors: K
authors: Kanamura
authors: Mine
authors: M
authors: Kinoshita
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004566:Electrodes; D004867:Equipment Design; D005240:Feasibility Studies; D007478:Iontophoresis / Q000295:instrumentation; D008297:Male; D008954:Models, Biological; D009270:Naloxone / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D018030:Silver Compounds / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine; D057968:Transdermal Patch
chemical_list: D009292:Narcotic Antagonists; D018030:Silver Compounds; D009270:Naloxone; C037548:silver chloride