Loxotop Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: After being absorbed transdermally, loxoprofen sodium hydrate is biotransformed into an active metabolite trans-OH form (SRS coordination) to exert its anti-inflammatory and analgesic effects in acute inflammations, chronic inflammations and pain.
Anti-inflammatory effects: LOXOTOP PAP 100 mg Patch has been demonstrated significant anti-inflammatory effects on both acute inflammations such as carrageenan-induced edema (rat) and chronic inflammations such as adjuvant arthritis (rat).
Analgesic effects: LOXOTOP PAP 100 mg Patch has been demonstrated to show the analgesic effect in the Randall-Selitto test (inflamed paw pressuring method: rat), and in the chronic adjuvant arthritis pain test (rat).
Pharmacokinetics: Plasma Concentration: Each of 14 Japanese healthy male adult volunteers was subjected to repeated administration of two LOXOTOP PAP 100 mg Patch on the back once a day for five days, showing detection of loxoprofen and its trans-OH form (active metabolite) in the plasma immediately after the start of the administration with their plasma concentrations gradually increasing over the period of the administration before reaching steady state in four or five days after the administration at low levels compared to those achieved by the equivalent oral dose of the same drug until, upon the discontinuation of the administration, they rapidly disappeared from the plasma to concentrations below the limit of quantitative determination (LQD).
Tissue Penetration: Administration of 3.5 cm² of the LOXOTOP PAP 100 mg Patch (containing ¹⁴C-loxoprofen) to the rat dorsal skin for a time period of 24 hours showed that the concentration of radioactivity in the skeletal muscle immediately under the patch administered area of the skin was 3.6- to 24-fold higher than that in the skeletal muscle under the patch non-administered area of the skin, confirming the formation of the trans-OH form of ¹⁴C-loxoprofen as its active metabolite.
Metabolism: An in vitro test of loxoprofen sodium hydrate for metabolism inhibition using human hepatic microsome showed that the drug did not inhibit the metabolism of substrates for cytochrome P450 enzymes (CYP1A1/2, 2A6, 2B6, 2C8/9, 2C19, 2D6, 2E1 and 3A4) even at a concentration of 200 μM equivalent to 1,000 times or more than the maximum plasma concentration observed by administration of LOXOTOP PAP 100 mg Patch in a dose of one patch a day.
Urinary Excretion: Each of 14 Japanese healthy male adult volunteers was subjected to repeated administration of two LOXOTOP PAP 100 mg Patch on the back once a day for five days, showing that the daily urinary excretion of loxoprofen, its trans-OH form (active metabolite) and cis-OH form remained almost constant after the elapse of 24 hours following the administration with the total cumulative excretion rate of 2.67% from the start of the administration until 48 hours after the discontinuation of the administration.