Percutaneous penetration of felbinac after application of transdermal patches: relationship with pharmacological effects in rats.
We have evaluated the percutaneous penetration of felbinac following application of topical patches using a microdialysis technique, and have examined correlations with pharmacological effects. A linear microdialysis probe with a 20-mm dialysis fibre was inserted into the skin of anaesthetized rats. Probe perfusion was started at 2.0 microL min(-1) with physiological saline and after a 60-min baseline sampling of dialysate, 0.1 mL croton oil was applied to the skin surface at a concentration of 8%, v/v. A felbinac patch was then applied to the same point 60 min thereafter and dialysate was sampled at 60-min intervals up to 300 min after patch application, for determination of concentrations of felbinac and prostaglandin (PG) E2. Analgesic effects of felbinac patches in an iodoacetateinduced osteoarthritis model and an incisional pain model were evaluated using the weight bearing method. After application of patches, felbinac penetration into the skin was rapid, maximum concentrations in the dialysates with 0.07, 0.5 and 3.5% w/w felbinac patches being 0.046+/-0.02, 0.104+/-0.06 and 0.244+/-0.2 microg mL(-1), respectively. Dermal administration of croton oil caused an increment in PGE2 levels, which was significantly decreased by 0.5 and 3.5% felbinac patches 2-5 h after application. In pharmacological studies, 3.5% felbinac patches suppressed pain-associated behaviour induced by iodoacetate injection and plantar incision. These results suggested that the transdermal patch containing 3.5% felbinac may become a useful formulation.
Shinkai
Norihiro
N
Research Department, Saitama Daiichi Pharmaceutical Co., Ltd, 8-1 Minamisakae-cho, Kasukabe, Saitama 344-0057 Japan. shinkai@sdsk.co.jp
Korenaga
Kazuko
K
Takizawa
Hiromi
H
Mizu
Hideo
H
Yamauchi
Hitoshi
H
D000279:Administration, Cutaneous; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D007719:Knee Joint / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D017551:Microdialysis / Q000379:methods; D023421:Models, Animal; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology; D010648:Phenylacetates / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D014950:Wounds, Penetrating / Q000188:drug therapy
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010648:Phenylacetates; C012776:biphenylylacetic acid; D015232:Dinoprostone