title: Pharmacokinetics of loxoprofen and its active metabolite after dermal application of loxoprofen gel to rats.
abstract: This study was conducted to evaluate the pharmacokinetics of loxoprofen (LX) and its active metabolite (trans-OH form) after a single dermal application of LX gel (LX-G) to rats. In the skin at the treated site, generation of the trans-OH form was detected and both LX and the trans-OH form remained at high concentrations for 24 h after dermal application. Furthermore, both LX and the trans-OH form also remained in the skeletal muscle over 24 h after the single dermal application, while they eliminated rapidly after the single oral administration. The area under the curve up to the last measurable point (AUC(0-t)) for plasma concentrations of LX or the trans-OH form after dermal application of LX-G was less than 11% of that after oral administration of LX. In addition, C(max) and AUC(0-t) increased in a saturable manner while increasing the dose. Overall, these results demonstrated that the trans-OH form was generated at the treated site with the process of dermal absorption of LX and it remained at the target site for a long period with low systemic exposure compared to oral administration.
authors.forename: R
authors.initials: R
authors.lastname: Sawamura
authors.forename: M
authors.initials: M
authors.lastname: Kazui
authors.forename: A
authors.initials: A
authors.lastname: Kurihara
authors.forename: T
authors.initials: T
authors.lastname: Izumi
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005782:Gels; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D009824:Ointments; D010666:Phenylpropionates / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption; D014018:Tissue Distribution
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005782:Gels; D009824:Ointments; D010666:Phenylpropionates; C040656:loxoprofen