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目的:研究重组单链尿激酶型纤溶酶原激活剂(rhscuPA)单链和代谢物双链(tcuPA)的药代动力学和转化。方法:125I标记结合生化反应及RPHPLC测定血浆125IscuPA和125ItcuPA浓度;平板溶圈法测定血浆溶纤组分浓度。结果:兔iv125IscuPA后单链呈双指数消除,T1/2α和T1/2β分别为7和43min,双链呈单指数消除T1/2=9min,约有38%单链转化为双链。猕猴静脉推注不同剂量rhscuPA后血浆纤溶组分浓度呈单指数下降,T1/2分别为(63±18)min,(115±21)min和(123±29)min,CLS随剂量变慢。推注ntcuPAT1/2=(137±27)min。结论:兔iv125IscuPA后可检测到125IrhscuPA与125ItcuPA。猕猴ivrhscuPA后血浆溶纤组分浓度呈非线性变化。
AIM: To study the pharmacokinetics and transformation of recombinant single chain urokinase-type plasminogen activator (rhscuPA) single-stranded and metabolite double-stranded (tcuPA). Methods: Plasma 125IscuPA and 125ItcuPA concentrations were determined by 125I labeling combined with biochemical reactions and RPHPLC. The concentration of plasma fibrinolysis was measured by platelet-dissolving method. Results: The single chain of iv125IscuPA was eliminated by double exponential method. The T1 / 2α and T1 / 2β were 7 and 43 min respectively. The double strand showed a single exponential elimination of T1 / 2 = 9 min. About 38% of single strands were converted into double strands. The concentration of fibrinolytic fraction in rhesus monkeys after intravenous administration of rhscuPA decreased by (63 ± 18) min, (115 ± 21) min and (123 ± 29) min, respectively . Bolus ntcuPAT1 / 2 = (137 ± 27) min. Conclusion: 125I rhscuPA and 125ItcuPA can be detected after iv125IscuPA in rabbits. After ivrhscuPA, the concentration of plasma fibrinolysis changed nonlinearly.