消化管運動調律薬 Trimebutine Maleate のラット及びマウスにおける代謝尿、胆汁及び血漿中代謝物の定性及び測定

概要

論文の詳細を見る
(±)-2-Dimethylamino-2-phenylbutyl 3,4,5-trimethoxybenzoate hydrogen maleate (trimebutine maleate. I) or _<14>C-labeled I was orally administered to rats and mice, and its metabolites in the urine, bile and plasma were fractionated, characterized and quantified.In both species, I was rapidly metabolized and main urinary metabolites were alcoholand acid-moiety metabolites formed by ester hydrolysis, i.e., 2-dimethylamino-2-phenyl-butanol (II) and its N-mono- and di-demethylated forms (III and IV), 3,4,5-trimethoxy-benzoic acid (V) and their conjugates.The proportion of the demethylated metabolites among the urinary metabolites was higher in mice than in rats.In the bile, metabolites considered to be O-and N, O-demethylated metabolites of I and their rearranged products of the latter were detected in a conjugated form beside the above urinary metabolites.The most abundant biliary metabolite was a conjugate of II in rats and that of N, O-di-demethylated I in mice. In the plasma, N-mono- and di-demethylated derivatives (VI, VII) of I were detected.The concentration of V in the plasma was by far the highest, followed by those of the alcohol-moiety metabolites, and the concentrations of I, VI and VII were very low.
公益社団法人日本薬学会の論文
1988-10-25