title: Intra-articular penetration of ketoprofen and analgesic effects after topical patch application in rats.
abstract: The purpose of this study was to evaluate percutaneous penetration and pharmacological effects of ketoprofen after transdermal administration, compared to the oral route. Skin and knee joint penetration of ketoprofen was tested by a microdialysis technique in rats and in vivo recovery was determined by retrodialysis. After oral and transdermal administration of ketoprofen, dialysate was sampled at 60 min intervals up to 360 min, for determination of concentrations of ketoprofen and prostaglandin E2. Analgesic effects of ketoprofen in iodoacetate and adjuvant-induced arthritis models were evaluated using the weight bearing method. The average recoveries of ketoprofen over 360 min in the skin and knee joint were 60.2+/-3 and 15.8+/-9%, respectively. Cmax values for ketoprofen absorbed within the skin after oral and transdermal administration were 20.1+/-5 and 297.5+/-478 ng/mL, respectively, and within the knee joint, 4.4+/-0.4 and 2.7+/-0.9 ng/mL. The Cmax value for the plasma concentration of ketoprofen after oral administration was approximately 80 times higher than with the transdermal route. Both transdermal and oral administration of ketoprofen significantly decreased PGE2 production in the skin and knee joint and improved weight bearing after exposure to iodoacetate and adjuvant. These results indicate that the transdermal ketoprofen patch is a useful formulation that can deliver the drug in sufficient amounts to inhibit prostaglandin E2 production in the skin and knee joint.
authors.affiliation: Research & Development Department, Nipropatch Co., Ltd., 8-1, Minamisakae-cho, Kasukabe, Saitama 344-0057, Japan. shinkai@nipro-patch.co.jp
authors.forename: Norihiro
authors.initials: N
authors.lastname: Shinkai
authors.forename: Kazuko
authors.initials: K
authors.lastname: Korenaga
authors.forename: Hideo
authors.initials: H
authors.lastname: Mizu
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yamauchi
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D007660:Ketoprofen / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D020370:Osteoarthritis, Knee / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D014018:Tissue Distribution
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007660:Ketoprofen