3H-莪术醇在正常大鼠及肿瘤小鼠体内的代谢研究

³H-莪术醇自大鼠胃肠道吸收迅速且完全。灌胃后5分钟血中即有放射性,15分钟达高峰,1小时仍保持较高浓度,放射性自血中消失的生物半衰期为11.5小时(t_(1/2)β)。静脉注射后血中放射性的消失分快、慢两相,生物半衰期分别为33分钟(t_(1/2)α)及12.5小时(t_(1/2)β)。放射性在正常大鼠体内分布情况与肿瘤小鼠者相似。肝及肾组织含量约为其它组织的2～2.5倍。肿瘤组织中的分布与其它组织无明显差别;组织中放射性的消失与血浆中者略呈平行关系。放射性与脂肪组织似有较强的亲和力,给药后4小时仍维持较高水平。放射性主要自尿排泄,口服或静脉注射后24小时分别自大鼠尿排出剂量的45.38%及51.91%。胆汁为另一排泄途径,大鼠口服或静脉注射后24小时,分别自胆汁排出36.47%及56.43%,而口服或静脉注射后72小时仅从粪回收6.77%及14.35%,可见,自胆汁排出的放射性大部分均又被重吸收入血。

THE METABOLISM OF 3H-CURCUMOL IN NORMAL RATS AND TUMOUR BEARING MICE

Absorption of ³H-Curcumol from gastrointestinal tract in rats was rapid and complete. Radioactivity could be detected from the blood 5 minutes after oral administration, and reached its peak level within 15 minutes. The blood level declined gradually with a half life (t 1/2 β) of 11.5 hrs. After iv injection of ³H-curcumol, the blood level of radioactivity was found to decrease in two phases with half lives of 33 rain. (t 1/2 α) and 12.5 hrs. (t 1/2 β) respectively.Tissue distribution study in rats revealed that the radioactivity was more or less evenly distributed in various organs including the heart, muscle, lung, plasma, brain, testis and spleen except for the liver and kidney which contained radioactivity 2～2.5 times higher. The tissue concentration decreased in a rate similar to that of the blood, with the exception of the adipose tissue which seemed to have a tendency to keep the radioactivity in a constant level for over 4 hrs. The pattern of tissue distribution of ³H-curcumol in turnout bearing mice was similar to that in normal rats, and the concentration in turnout tissue was found to be similar to that in other tissues.Kidney seemed to be the main route of clearance. About 45.38% or 50.91% of the dose could be recovered in urine 24 hrs, after oral or iv administration. Biliary tract was another route of excretion. Twenty four hrs after oral or iv administration, about 36.47% or 56.43%, respectively, of the dose were recovered from the bile collected from the biliary fistula. However, the amount excreted in faeces constituted only 6.77% or 14.35% of the dose even 72 hrs after its oral or iv administration, suggesting that most of the radioactivity excreted from the bile was reabsorbed from the gastrointestinal tract in the intact animals.