ウサギにおけるNitrazepamの尿中新代謝産物と生体内変化

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The structures of four hitherto unidentified metabolites of nitrazepam in the rabbit were elucidated using ultra violet (UV), infrared (IR), nuclear magnetic resonance (NMR) and mass spectrometry. They were 2'-benzoyl-2-hydroxy-4'-nitroacetoanilide (M-I), hydroxylated 2-amino-5-nitrobenzophenone (M-II), 7-amino-8-hydroxynitrazepam (M-III) and 2-formamido-5-nitrobenzophenone (M-IV). These metabolites were excreted primarily in conjugated from except for M-IV. Urinary excretion of nitrazepam and its metabolites were studied by preparative thin-layer chromatography (TLC) and characteristic colorimetric methods before and after enzymic hydrolysis of the conjugates. 2-amino-3-hydroxy-5-nitrobenzophenone (3-OH-ANB) was the major metabolite following oral administration. The excretion of 7-amino-nitrazepam and 7-acetamidonitrazepam increased, but that of 3-OH-ANB decreased following intraperitoneal administration. In both types of administration, M-I to IV were minor metabolites (about 1% of the dose), but M-I and M-IV were considered to be intermediates leading to 2-amino-5-nitrobenzophenone. On the basis of these data, the metabolic pathways of nitrazepam in the rabbit were postulated in Chart 1.
公益社団法人日本薬学会の論文
1979-01-25