心脈管系薬に関する研究(第3報) : 8-[(1,4-Benzodioxane-2-yl)methyl]-3-oxo-1-thia-4,8-diazaspiro(4,5)decane Maleate(Y-3506)の吸収, 生体内分布, 排泄および代謝

抄録

Tritium-labeled compound of a new benzodioxane derivative, 8-[(1, 4-benzodioxane-2-yl) methyl]-3-oxo-1-thia-4, 8-diazaspiro (4, 5) decane maleate (Y-3506), was administered to rats orally, intraperitonealy, intravenously or intramuscularly. About 50% and 40% of the administered radioactivity (³H) were excreted in the urine and feces, respectively, by any route within 3 days. Following oral administration, 57% of the dose was also excreted in the bile during 24 hours. The highest concentration of ³H in most organs was found from 0.5 to 1 hour after oral administration, and the levels of ³H in the liver, adrenals, kidney, and serum were high, but those in the adipose tissue and brain were relatively low. Concentration of ³H in the adipose tissue was high in the case of intravenous administration. Protein binding of ³H in the serum was 15%. About 70% or more of ³H in the tissues other than the liver was attributable to S-oxide of Y-3506, one of the metabolites of Y-3506, and less than 20% to the unchanged Y-3506, 30 min after oral administration. On the other hand about 50% of ³H was found to exist as the unchanged compound in the blood and liver, 15 min after intravenous administration. Y-3506-S-oxide was identified as the major metabolite in 24-hour urine. Urinary excretion of the unchanged compound in the case of intravenous administration was more than that in the case of oral administration.