Pharmacokinetics of loxoprofen and its active metabolite after dermal application of loxoprofen gel to rats.

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.