Metabolism of Benzydamine Hydrochloride : Species Differences and the Identification of Unconjugated Metabolites in Rabbit Urine

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The urinary metabolites of benzydamine hydrochloride (BZY・HCl) in rabbits were isolated by the combination of extraction with CHCl_3 and column or thin-layer chromatography on Amberlite XAD-2,silica gel, and aluminum oxide, and identified by thin-layer co-chromatography with authentic samples and by mass and nuclear magnetic resonance spectroscopy. The major two metabolites are benzydamine N-oxide (BZY-NO) and 1-(p-hydroxybenzyl)-3-(3-dimethylaminopropoxy)-1H-indazole (HO-BZY). The minor others are demethylated BZY (nor-BZY), N-debenzylated BZY (deB-BZY), 1-benzyl-1H-indazolone (BID), and indazolone (ID). The excretion of unchanged BZY amounts about 1%. In addition, three glucuronides were found but their chemical structures are not clarified, yet. The total amount of fluorescent metabolites excreted in 24 hr urine of rat, mouse, guinea pig, rabbit and dog received BZY・HCl was equivalent to around 30% of dose. However, 62.4 or 74.7% of fluorescent metabolites of rat or dog was extracted directly with chloroform but about 20% of mouse, guinea pig or rabbit were. After incubating chloroform extracted urine with β-glucuronidase, the fluorescent metabolites in urine was extracted with chloroform more than 70% in mouse, guinea gig or rat but less than 40% in rabbit and 10% in dog. The cat excretes fluorescent metabolites equivalent to 16.6% of dose and no glucuronide.
公益社団法人日本薬学会の論文
1973-02-25