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标题：Enzymologic and Pharmacologic Profile of Loxoprofen Sodium and Its Metabolites
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作者：Masahiro Noguchi ; Aishi Kimoto ; James Kevin Gierse 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2005
卷号：28
期号：11
页码：2075-2079
DOI：10.1248/bpb.28.2075
出版社：The Pharmaceutical Society of Japan
摘要：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.
关键词：loxoprofen sodium;cyclooxygenase;prostaglandin;non-steroidal anti-inflammatory drug (NSAID)