一种新静脉注射肝脏造影混悬制剂-TABAC-的药物代谢动力学研究

2,4,6三碘-3-乙酰胺基苯甲酸-N-环己胺甲酰氧基乙酯是一种新肝脏造影剂,简称TABAG。本文报道用同位素¹³¹Ⅰ标记TABAC并将其制成混悬制剂,在大白鼠体内进行药物代谢动力学研究。根据血药-时间曲线形状符合二室开放模型,其动力学关系式为C=5.51e^0.0538t+0.245e^-0.00221t 从动力学参数K₁₂与K₂₁值表明,正向转运速度比逆向转运速度大5.6倍。肝脏药量-时间曲线显示药物迅速进入肝脏,其摄取峰区域在注射后15分钟到2小时之间,与X线摄影结果相符合。24小时以后,肝脏含药量只剩注入量的8%,两天后降到注入量的3%左右。用药96小时后,该药71%以上由大小便排出。从各脏器内药量分布图表明,肝脏含药量比例最高。在摄取峰值时,肝内药量约占注入量的70%,肺、心、肾内含药量很少。说明药物可以迅速浓集在肝脏,从而初步证实利用肝脏网状内皮组织吞噬作用来设计肝脏造影剂的设想是成功的。这种设想及其新型制剂有助于制剂的定向发展。

PHARMACOKINETIC STUDIES ON THE INTRAVENOUS SUSPENSION OF A NEW HEPATOSPLENOGRAPHY AGENT

The suspension of 2,4,6, -triiodo-3-acetamidobenzoic acid(N-cyclohexyl carbamyloxy) ethyl ester (TABAC) is a new hepatosplenography agent which is administered intra-venously. The pharmacokinetics of the ¹³¹Ⅰ labeled TABAC suspension was investigated in rats.After the suspension was given intravenously to rats, the blood radioactivity level decreased very rapidly followed by a slow decreasing period. It showed the characteristics of two biological phases, the distribution phase and the elimination phase. According to the shape of blood level curve, 2-compartment open model could be fitted and the kinetic expression of blood level curve could be described byC=5.51 e^-0.0583t+0.245 e^-0.00221t The liver radioactivity level of the drug after intravenous administration to rats rose very rapidly, and an absorption peak appeared in 45 minutes after injection. The kinetic expression of liver drug-time curve could be described byC=55.5e^-0.00125t+27.0e^-0.0171t-77. 0e^-0.151t The distribution studies of the drug in different organs after i.v. administration to rats showed that the highest radioactive level was found in the liver and it approximated 70% of the total administered dose. In comparison with liver, the radioactivity in spleen, lungs, heart and kidneys was found to be relatively lower.Up to 96 hours after injection about 44.7% of the administered radioactivity were excreted in the urine, while about 26.7% were found in feces.