title: In-vitro and in-vivo transdermal iontophoretic delivery of tramadol, a centrally acting analgesic.
abstract: OBJECTIVE
  The feasibility of transdermal delivery of tramadol, a centrally acting analgesic, by anodal iontophoresis using Ag/AgCl electrodes was investigated in vitro and in vivo.
  
  
  METHODS
  To examine the effect of species variation and current strength on skin permeability of tramadol, in-vitro skin permeation studies were performed using porcine ear skin, guinea-pig abdominal skin and hairless mouse abdominal skin as the membrane. In an in-vivo pharmacokinetic study, an iontophoretic patch system was applied to the abdominal skin of conscious guinea pigs with a constant current supply (250 µA/cm(2)) for 6 h. An intravenous injection group to determine the pharmacokinetic parameters for estimation of the transdermal absorption rate in guinea pigs was also included.
  
  
  RESULTS
  The in-vitro steady-state skin permeation flux of tramadol current-dependently increased without significant differences among the three different skin types. In the in-vivo pharmacokinetic study, plasma concentrations of tramadol steadily increased and reached steady state (336 ng/ml) 3 h after initiation of current supply, and the in-vivo steady-state transdermal absorption rate was 499 µg/cm(2) per h as calculated by a constrained numeric deconvolution method.
  
  
  CONCLUSIONS
  The present study reveals that anodal iontophoresis provides current-controlled transdermal delivery of tramadol without significant interspecies differences, and enables the delivery of therapeutic amounts of tramadol.
authors: Department of Device Development, TTI ellebeau, Inc., Higashi-Shinagawa, Shinagawa-ku, Tokyo, Japan.
authors: Shinri
authors: S
authors: Takasuga
authors: Rie
authors: R
authors: Yamamoto
authors: Shoichi
authors: S
authors: Mafune
authors: Chiyo
authors: C
authors: Sutoh
authors: Katsuya
authors: K
authors: Kominami
authors: Yoshimasa
authors: Y
authors: Yoshida
authors: Masao
authors: M
authors: Ito
authors: Mine
authors: M
authors: Kinoshita
mesh_terms: D000279:Administration, Cutaneous; D000701:Analgesics, Opioid / Q000493:pharmacokinetics*; D000818:Animals; D006168:Guinea Pigs; D007478:Iontophoresis / Q000379:methods*; D051379:Mice; D023421:Models, Animal; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine; D014147:Tramadol / Q000493:pharmacokinetics*
chemical_list: D000701:Analgesics, Opioid; D014147:Tramadol