1-Tertiary-butylamino-3-(2,3-dimethylphenoxy)-2-propanol(D-32), 新β-遮断剤の代謝(第2報)血中濃度, 分布, 胆汁中の代謝物の構造

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The distribution, blood level, and biliary metabolites of D-32,a new adrenergic β-blocking agent, were investigated in rats, rabbits, and dogs using ^3H-labeled D-32. When D-32-^3H was administered intravenously to the rat, radioactivity was taken up by the lung in higher concentration than by other organs and then decreased gradually with time. In the lung and brain, the main radioactivity accumulated was due to D-32,whereas most part of it was present as metabolites in the liver and kidneys. After both intravenous and oral administration, the half-life in plasma was approximately 45 min in rats, but was of the order of 110-160 min in dogs and rabbits. After oral administration there was virtually a complete absorption and peak blood levels of D-32 and active metabolites, 4'-hydroxy-D-32 and 3'-hydroxymethyl-D-32,were seen at about 1.5 hr after the administration. Further these metabolites appeared in the blood in amounts equal to D-32. On the other hand, after intravenous administration, total amount of active metabolites was only 1-10% of D-32 in the blood. These findings demonstrate that D-32 is absorbed easily from the gastrointestinal tract and is rapidly metabolized in the liver. The rat excreted approximately 40% of the dose in the bile during 24 hr. The major metabolites obtained from the bile were identified as 4'-hydroxy-D-32 4-O-glucuronide and 3'-hydroxymethyl-D-32 3-O-glucuronide by chemical degradation, nuclear magnetic resonance and mass spectra. D-32 undergoes metabolism in the rabbit liver involving NIH shift migration of the deuterium on metabolic 4'-hydroxylation of 4-deuterated D-32.
公益社団法人日本薬学会の論文
1975-06-25

1-Tertiary-butylamino-3-(2,3-dimethylphenoxy)-2-propanol(D-32), 新β-遮断剤の代謝(第2報)血中濃度, 分布, 胆汁中の代謝物の構造

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