国产基因重组人尿激酶型原(Pro-urokinase/u-PA)Ⅰ期临床安全性、耐受性研究  

The Tolerance and the Safety of Genetic Recombinant Human Glycosylated Single-Chain Pro- Urokinase(u-PA) and Its Effects on the Fibrinolytic Parameters in Chinese Healthy Adults

作　　者：王禹[1] 李天德[1] 孙中华[1] 余霞君[1] 张正光[2] 胥照平[2] 

机构地区：[1]解放军总医院心血管内科,北京100853 [2]军事医学科学院生物工程研究所,北京00071

出　　处：《中国临床药理学杂志》2002年第6期410-413,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的:对国内研制的注射用基因重组人尿激酶型纤溶酶原激活剂（Pro-urokinase,u-PA）进行Ⅰ期临床试验,以评价其用于中国健康成人受试者的安全性和耐受性。方法:试验日期;健康受试者23例（男11例,女12例）,随机分为5,20,35mg和50mg四个剂量组。静脉给药:其中1/4剂量在1min内静脉推注,其余3/4剂量在60min内静脉滴注完毕。给药前和给药后2,24h取外周血测定血液生化指标、凝血和纤溶指标,并随时观察受试者的全身状态和可能出现的药物不良反应。结果:全部受试者用药前后的血压,心率/律、呼吸等重要生命体征未见异常变化;血、尿常规、肝肾功能,电解质、空腹血糖等亦未见明显变化。与溶栓有关的血液学指标（活化的部分凝血活酶时间,凝血酶原时间,凝血酶原活动度,纤维蛋白原,α2-抗纤溶酶和纤维蛋白降解产物）,在部分受试者有改变,但变化均在正常范围内、且与剂量无明显相关,无明确临床意义。全部受试者注射药物的局部皮肤,无刺激性炎症和皮下淤血、出血等变化。结论:中国健康成人受试者对于上述剂量的基因重组人尿型纤溶酶原激活剂的安全性及耐受性良好。OBJECTIVE: To evaluate the tolerance, safety and the effects on the fibrinolytic system of the genetic recombinant human glycosylated single-chain pro-urokinase (u-PA) in healthy Chinese adults. METHODS: genetic recombined u-PA was injected intravenously for 23 Chinese healthy volunteers who were divided into four dose-groups randomizely: 5, 20, 35, 50mg. RESULTS: There were no abnormal changes in blood pressure, heart rate, heart rhythm, and respiration rate and other major physical signs in all subjects. There were also no significant difference in blood biochemical parameters related to thrombolysis (prothrombin time, activated partial thromboplastin time, fibrinogen, plasminogen, a2-anti-plasmin),and also no statistic difference in blood and urine examination, hepatic and renal functions, electrolytes, blood glucose and other major biochemical parameters. No bleeding complications and other major side-effects were found in all 23 cases. CONCLUSION: In Chinese healthy adult volunteers, the use of genetic recombinant human glycosylated single-chain urokinase-type plasminogen activator/u-PA intravenously have a good tolerance and no significant complications were found.

关 键 词：基因重组人尿型纤溶酶原激活剂 Ⅰ期临床试验 药物安全性 耐受性 溶检药 

分 类 号：R927.11[医药卫生—药学] R977