Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Enzymologic and Pharmacologic Profile of Loxoprofen Sodium and Its Metabolites
Masahiro NoguchiAishi KimotoJames Kevin GierseMark Crossfield WalkerBen Scott ZweifelKazutoshi NozakiMasao Sasamata
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2005 Volume 28 Issue 11 Pages 2075-2079

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Abstract

We investigated the mechanism of inhibition of loxoprofen sodium, a non-steroidal anti-inflammatory drug (NSAID), and its active metabolite (loxoprofen-SRS) on cyclooxygenase (COX). In in vitro assays, loxoprofen sodium appeared inactive against recombinant human COX-1 and COX-2, whereas loxoprofen-SRS inhibited both. In the investigation of kinetic behavior, loxoprofen-SRS showed time-dependent inhibition for both isozymes. Human whole blood assay also showed that loxoprofen-SRS possesses the profile of a non-selective inhibitor for COX. In a rat air pouch model, oral administration of loxoprofen sodium lowered prostaglandin (PG) E2 in both fluid exudates of the inflammatory pouch and stomach tissue with ED50 values of 2.0 and 2.1 mg/kg, respectively. Additionally, platelet thromboxane B2 production was also inhibited by loxoprofen sodium (ED50 of 0.34 mg/kg). In a rat carrageenan-induced paw edema model, loxoprofen sodium dose-dependently reduced the paw edema, accompanied by a decrease in PGE2 content in inflamed paw exudates. These findings suggest that the COX inhibitory activity of loxoprofen sodium is attributable to its active metabolite, loxoprofen-SRS, and that loxoprofen-SRS shows non-selective inhibition for COX.

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© 2005 The Pharmaceutical Society of Japan
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