向精神薬に関する研究(第7報) : APY-606の生体内運命その2^3H-APY-606の吸収, 生体内分布, 排泄および代謝

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Tritium labeled compound (^3H-APY-606) of a new phenothiazine derivative, 8-[3-(2-chloro-10-phenothiazynyl) propyl]-3-oxo-1-thia-4,8-diazaspyro [4,5] decane hydrochloride was synthetized, and its absorption, distribution, excretion and metabolism were investigated in rats. When this compound was orally administered at a dose of 10 mg/kg, about 40% of the dose was absorbed from the gastrointestinal tract within 6 hr, but the speed of absorption was relatively slow. 3% and 55% of the administered radioactivity (^3H) were excreted in the urine and feces, respectively, during the 3 days following the oral administration of ^3H-APY-606,and 32% of the dose was also excreted in the bile during 24hr. The highest concentration of ^3H in most organs was found 4 hr after its oral administration, and ^3H was concentrated in the liver, adrenals, kidney and lung. ^3H level in the brain was 2-4 fold of that in the blood, and blood level was relativery low. Protein binding of ^3H in the serum was 90% at 1 hr, 34% at 24 hr, after oral administration. Seventy % of ^3H in the urine and 94% of it in the bile were extracted with organic solvent, and a small amount of glucuronide was formed in the urine. Four radioactive metabolites in the urine and 3 metabolites in the bile were detected by thin-layer chromatography, but the native compound could not be detected.
公益社団法人日本薬学会の論文
1970-07-25