放射性同位元素による医薬品の分析(第9報)ラットにおけるd-およびl-エフェドリンの体内分布および体内代謝産物の同定

抄録

The distribution of d- and l-ephedrine[α-¹⁴C] in rats was studied by whole body autoradiography, and the metabolites in organs, in which high radioactivity was detected, were identified by the reverse isotope dilution analysis. Amount of radioactivity at 2.5 hr after subcutaneous injection decreased in the order of liver, kidney>brain, spleen, adrenal, lung, contents of stomach and intestine. In addition, it was found that the levorotatory isomer has a stronger affinity for organs and is more slowly excreted in urine than the dextrorotatory isomer. In the liver, norephedrine, p-hydroxyephedrine, and glucuronides of ephedrine and p-hydroxyephedrine were identified as the metabolites together with unchanged ephedrine, while almost all radioactivity in the brain and the spleen was explained as that of the substrate itself. From the comparison of recovered metabolites, it was found that the d-isomer is less liable to be metabolized than the l-isomer. Moreover, it was revealed that deaminaiton and p-hydroxylation are greatly affected by configuration in the α-position and so require greater stereospecifisity than N-demethylation reaction.