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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 conduct a phase I clinical trial of a recombinant human urokinase-type plasminogen activator (u-PA) for injection in China to evaluate its safety and efficacy in Chinese healthy adult subjects Tolerance. Methods: The test date; 23 healthy subjects (11 males and 12 females) were randomly divided into 4 doses of 5, 20, 35 mg and 50 mg. Intravenous administration: One quarter of the dose within 1min intravenous injection, the remaining 3/4 dose within 60min intravenous infusion is completed. Peripheral blood samples were taken for determination of blood biochemistry, coagulation and fibrinolysis before administration and 2, 24 hours after administration, and the status of the subject and possible adverse drug reactions were observed at any time. Results: All subjects had no significant changes of vital signs such as blood pressure, heart rate / pulse and respiration before and after treatment. No significant changes were observed in blood, urine, liver and kidney function, electrolytes and fasting blood glucose. Thrombolytic-related hematologic parameters (activated partial thromboplastin time, prothrombin time, prothrombin activity, fibrinogen, alpha 2-antiplasmin, and fibrin degradation products) were measured in some subjects There are changes, but the changes are within the normal range, and no significant correlation with the dose, no clear clinical significance. All subjects were injected with topical skin, non-irritating inflammation and subcutaneous congestion, bleeding and other changes. CONCLUSIONS: The safety and tolerability of recombinant human urokinase plasminogen activator in Chinese healthy adult subjects at these doses is good.