4'-Chloro-5-methoxy-3-biphenylylacetic Acid (DKA-9) のラットにおける代謝および抗炎症作用に関する研究

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The metabolic fate of 4'-chloro-5-methoxy-3-biphenylylacetic acid (DKA-9), a newly developed anti-inflammatory drug, was examined in rats after intravenous administration of ^<14>C-DKA-9. It was found that DKA-9 was metabolised mainly through two major pathways, glucuronide formation and demethylation followed by sulfate formation. The matabolites in urine and bile were fractionated by the combination of solvent extraction and preparative thin-layer chromatography. Five metabolites were detected and the structure of these metabolites was investigated from spectral and elemental analysis data. The major metabolites were identified as potassium 4'-chloro-5-hydroxy-3-biphenylylacetic acid O-sulfate (72.4% of the dose in 24 hr) in urine, 1-(4'-chloro-5-methoxy-3-biphenylylacetoxy) glucuronic acid (28.0% of the dose in 6 hr) in bile, and DKA-9 (5.2% of the dose in 48 hr) in feces, and the minor metabolites were also identified as 4'-chloro-5-hydroxy-3-biphenylylacetic acid, 2-(4'-chloro-5-methoxy-3-biphenylyl)-2-hydroxyacetic acid and (4'-chloro-5-methoxy-3-biphenylylacetyl) glycine. The anti-inflammatory action of DKA-9 and its metabolites were also investigated by the inhibition of carrageenin-induced edema. There was no active metabolite and, therefore, the anti-inflammatory effect of DKA-9 in the rat seemed to be due to the action of DKA-9 itself.
公益社団法人日本薬学会の論文
1978-01-25