Evaluation of percutaneous permeation of flurbiprofen and ketoprofen after application of transdermal patches using a lateral sectioning approach in hairless rats.
OBJECTIVE
The dispositions and pharmacokinetic parameters of non-steroidal anti-inflammatory drugs (NSAIDs) after patch applications have typically been evaluated on a whole-skin basis, and the detailed permeation profiles remain unclear. The aim of this study was to establish a new method for clearly analyzing the flow of drugs in the skin layers and evaluating the drug levels in the target area of the skin tissue.


METHODS
The skin tissue areas where flurbiprofen and ketoprofen patches were applied were cut into 20 μm-thick lateral slices from the surface to the deepest layer and the drug concentrations in the slices were measured.


RESULTS
The results revealed the presence of depth-dependent concentration gradients from the surface to the deep layer and that the drug concentration in the deepest layer was less than one tenth of the surface concentration for both flurbiprofen and ketoprofen. In addition, flurbiprofen yielded higher and more rapid concentrations in the deepest skin layer adjacent to the intramuscular tissue.


CONCLUSIONS
The present data suggest that our technique involving lateral slicing of skin tissues and measurement of drug concentrations allows visual understanding of drug dispositions in the skin layers and makes it possible to evaluate the drug levels in the target area of the skin tissue.
Goi
Nobuhiro
N
Research & Development Division, Mikasa Seiyaku Co. Ltd, Nerima-ku, Tokyo, Japan. goi2667@mikasaseiyaku.co.jp
Morishita
Katsunori
K
Taniguchi
Akihito
A
Ishii
Takayuki
T
Saitoh
Kiyoshi
K
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems; D005480:Flurbiprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007660:Ketoprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D010539:Permeability; D051381:Rats; D054772:Rats, Hairless; D012869:Skin Absorption; D014018:Tissue Distribution; D057968:Transdermal Patch
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005480:Flurbiprofen; D007660:Ketoprofen