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目的:研究比伐卢定注射液对健康志愿者纤维蛋白原和凝血酶时间的影响。方法:48名健康志愿者随机分为4个试验组,分别为静脉注射比伐卢定0.5,0.75和1.05 mg.kg-1组以及以0.75 mg.kg-1静脉推注后,立即续以1.75 mg.kg-1.h-1的速度匀速静脉滴注4 h组。每组12人,其中9名给予比伐卢定注射剂,3名接受安慰剂。静脉注射组在给药前和给药后20 min,45 min,1 h,2 h,24 h和72 h,静脉推注加静脉滴注组在静脉推注前和静脉滴注开始后2,4,6,8,24和72 h,取血测定纤维蛋白原(fibrinogen,Fib)浓度和凝血酶时间(thrombin time,TT)。结果:比伐卢定剂量依赖性地延长TT,停药后2 h,TT值逐渐恢复正常。比伐卢定剂量依赖性地降低Fib浓度,尤其是静脉推注加静脉滴注组降低明显,但这可能是由于检测方法的影响,产生的假性降低现象。结论:在比伐卢定II期临床试验中,应密切监测受试者的凝血指标,注意观察受试者是否发生出血不良事件。在有直接凝血酶抑制剂存在时,应避免使用冯.克劳斯法检测Fib浓度。
Objective: To study the effect of bivalirudin injection on fibrinogen and thrombin time in healthy volunteers. Methods: Forty-eight healthy volunteers were randomly divided into four groups: 0.5, 0.75 and 1.05 mg.kg-1 for intravenous injection of bivalirudin, and intravenous injection of 0.75 mg.kg-1 1.75 mg.kg-1.h-1 speed uniform infusion 4 h group. Twelve in each group, 9 were given bivalirudin and 3 were given placebo. Intravenous injection group before intravenous injection and after 20 min, 45 min, 1 h, 2 h, 24 h and 72 h, intravenous injection plus intravenous infusion group before intravenous infusion and intravenous infusion started 2, At 4, 6, 8, 24 and 72 h, blood samples were collected for determination of fibrinogen (Fib) concentration and thrombin time (TT). Results: Bivalirudin dose-dependently prolonged TT, 2 h after withdrawal, TT values gradually returned to normal. Bivalirudin dose-dependently reduced the concentration of Fib, especially intravenous injection plus intravenous drip group decreased significantly, but this may be due to the impact of detection methods, resulting in false reduction phenomenon. CONCLUSIONS: In the phase II clinical trial of bivalirudin, the subjects should be closely monitored for coagulation parameters and attention should be paid to observe whether the subjects have bleeding-related adverse events. In the presence of direct thrombin inhibitors, von Klaus method should be used to detect Fib concentrations.