The Whole Body Autoradiographic Studies on the Distribution of ^<14>C-Labeled New 1,5-Benzothiazepine Derivative (^<14>C-CRD-401) in Mice

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The distribution of a ^<14>C-labeled coronary vasodilator, 3-acetoxy-2,3-dihydro-5-[2-(dimethylamino) ethyl]-2-(p-methoxyphenyl)-1,5-benzothiazepin-4 (5H)-one hydrochloride-(^<14>C-CRD-401), in mice was studied by means of whole body autoradiographic technique. Immediately after intravenous injection, ^<14>C-CRD-401 disappeared from the blood and accumulated in the heart muscle, lung, adrenal cortex, kidney, skeletal muscle and brain. The high radioactivity appeared rapidly in the stomach mucosa and bile, and consequently in the lumen of the stomach and intestine. Most organs which exhibited the highest radioactivity immediately after the injection showed gradually diminishing radioactivity during the first 24 hours. When administered orally to mice, ^<14>C-CRD-401 was rapidly and easily absorbed from the intestinal tract, and the radioactivity in various organs reached their maximal levels within 30 minutes. The experiments with pregnant mice administered ^<14>C-CRD-401 intravenously and orally demonstrated that there was a slow and slight penetration of radioactive materials to the fetuses through the placenta. Chromatographic investigation on the tissue-extracts of mice treated with ^<14>C-CRD-401 demonstrated the compound was rapidly metabolized in mice after intravenous administration as well as after oral one.

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