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第一部分 :采用交叉设计 ,自身比较 ,研究了猕猴静脉注射 0 .4 ,0 .8和 3.2mg·kg- 1 重组人尿激酶原 (rhprouk)或 1.2 8× 10 5IU·kg- 1 尿源性天然尿激酶 (un UK) (其中推注 15 %剂量 ,90min内恒速滴注 85 %剂量 )后血浆中单链尿激酶型纤溶酶原激活剂 (scu PA)和双链尿激酶型纤溶酶原激活剂 (tcu PA)的浓度随时间变化、代谢转化和各自的药代动力学 ,及代谢转化和药代动力学参数与剂量浓度的依赖关系 .结果表明给药后scu PA转化为tcu PA的速度与scu PA的剂量呈正相关性 .第二部分 :通过测定兔静脉推注加滴注1 2 5I rhprouk 0 .8mg·kg- 1 (其中 15 %剂量静脉推注 ,85 %剂量在 90min内滴注 ,比放射活性 2 .5 0 6MBq/mg)后不同时间体内各组织总放射性、TCA酸沉放射性 ,以及酸沉和总放射性的比值 ;胆汁引流物放射性累计排出量 ,尿和粪中累计排出量 ,及在体内外1 2 5I rhprouk与血浆蛋白的结合 .研究rhprouk在体内的分布、代谢及排泄情况 .结果表明rhprouk不与血浆中蛋白结合 ,代谢部位主要集中在胆、肾等部位 ,代谢产物主要随小便排出 .
The first part: Using crossed design, self-comparison, we studied the intravenous injection of 0.4, 0.8 and 3.2 mg · kg -1 recombinant human prourokinase (rhprouk) or 1.2 8 × 10 5 IU · kg -1 urinary Plasma un single-stranded urokinase-type plasminogen activator (scu PA) and double-stranded urokinase-type fibrillated fibroblasts after administration of un urokinase (15% bolus and 85% The changes of tcu PA concentration with time, metabolic transformation and their pharmacokinetics, and the dependence of metabolic transformation and pharmacokinetic parameters on dose concentration showed that scu PA was converted to The velocity of tcu PA was positively correlated with the dose of scu PA.Part II: The intravenous bolus injection of 125 I rhprouk 0. 8 mg · kg -1 (intravenous injection of 15%, 85% 90min instillation, than the radioactivity of 2.56 MBq / mg) at different times after the total radioactivity in vivo, TCA acid precipitation radioactivity, and the ratio of acid precipitation and total radioactivity; cumulative discharge of bile drainage, urine and feces In the cumulative excretion, and in vitro and in vivo 1 225 lipoprotein binding with plasma protein research rhprou k in vivo distribution, metabolism and excretion of rhprouk.The results show that rhprouk does not bind to plasma proteins, the metabolic sites mainly in the gallbladder, kidney and other parts of the main metabolites with urinary excretion.