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BIO-TRANSFORMATION AND PHARMACOKINETICS OF SINGLE CHAIN UROKINASE-TYPE PLASMINOGEN ACTIVATOR IN RABBITS AND RHESUS MONKEYS

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Author:
No author available
Journal Title:
ACTA PHARMACEUTICA SINICA
Issue:
2
DOI:
10.3321/j.issn:0513-4870.2000.02.004
Key Word:
单链尿激酶;双链尿激酶;反相高效液相色谱;125I标记;药代动力学;溶纤活性

Abstract: 目的:研究重组单链尿激酶型纤溶酶原激活剂(rh-sc-uPA)单链和代谢物双链(tc-uPA)的药代动力学和转化.方法:125I标记结合生化反应及RP-HPLC测定血浆125I-sc-uPA和125I-tc-uPA浓度;平板溶圈法测定血浆溶纤组分浓度.结果:兔iv 125I-sc-uPA后单链呈双指数消除,T1/2α和T1/2β分别为7和43 min,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rh-sc-uPA后血浆纤溶组分浓度呈单指数下降,T1/2分别为(6.3±1.8)min,(11.5±2.1)min和(12.3±2.9)min,CLS随剂量变慢.推注n-tc-uPA T1/2=(13.7±2.7)min.结论:兔iv 125I-sc-uPA后可检测到125I-rh-sc-uPA与125I-tc-uPA.猕猴ivrh-sc-uPA后血浆溶纤组分浓度呈非线性变化.

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