塩酸エプラジノンの生体内運命の研究(第3報)塩酸エプラジノンのラット肝酵素による酸化的N-C開裂について

概要

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An examinations was made to determine whether the previously known in vivo N-C cleavage of the Mannich base moiety of an antitussive, Eprazinone [1-(2-ethoxy-2-phenylethyl)-4-(2-benzoylpropyl) piperazine] takes place enzymically or nonenzymically. When the drug was incubated with phosphate buffer (pH 7.4) alone, whole blood of a rat, or a 9000×g supernatant of boiled rat liver in vitro, only a small extent of N-C cleavage occurred. However, the drug was cleaved significantly by its incubation with a 9000×g supernatant of a rat liver homogenate. The N-C cleavage of Eprazinone decreased in an anaerobic atmosphere or by incubation without NADP^+ and glucose 6-phosphate. Further, the enzyme with this activity was induced by treatment of rats with phenobarbital, and was inhibited by SKF 525-A in vitro. These results suggested that the N-C bond of Mannich moiety of Eprazinone was cleaved by an oxygenase in rat liver. It is of interest that Eprazinone was selectively cleaved at the N-C bond of its Mannich base moiety by a hepatic oxygenase.
社団法人日本薬学会の論文
1975-08-25