向精神薬に関する研究(第7報) : APY-606の生体内運命 その2³H-APY-606の吸収, 生体内分布, 排泄および代謝

抄録

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.