乌司他丁在中国健康成年受试者中的耐受性研究

发布时间：2019-01-12 15:23

【摘要】：目的探索注射用乌司他丁在中国健康成年受试者中单日多次给药的安全性、耐受性。方法采用随机、平行、双盲、安慰剂对照的1天多次给药研究设计,将24例健康受试者随机分为A、B、C 3个剂量组,每组8例,其中每组2名健康受试者作安慰剂对照,3个剂量组的安慰剂受试者合并为安慰剂组(n=6)。A组每次给药60万U,B组每次给药90万U,C组每次给药120万U,3组均1天4次,每两次给药间隔为3 h。首剂给药匀速缓慢推注30 min,其后的3次给药按每0.5 h滴注50万U的速度匀速静脉滴注。观察各剂量组的受试者在给药前后的生命体征变化、心电图检查结果、实验室各检查项目指标的变化以及异常值和不良事件。结果 24例受试者均完成试验。给药后实验室检查异常值中,仅C组和安慰剂组的5例纤维蛋白原降低为异常有临床意义,其他检查结果均为正常或异常无临床意义。试验中,未见严重不良反应。其中,A组和B组未发生任何不良事件。C组出现2例次与药物可能相关的轻度腹泻(2/6)、3例次与药物可能无关的纤维蛋白原偏低(3/6)和1例次与药物可能无关的脐周腹痛(1/6)。所有不良事件均为Ⅰ级,并且均在未采取任何措施的情况下自行缓解。结论注射用乌司他丁1天多次给药,在每天4次,每次60万U到120万U的给药范围内,安全性较好,受试者均可耐受。因此,建议后续临床使用剂量最高可达到每次120万U,每天4次。
[Abstract]:Objective to investigate the safety and tolerance of ulinastatin for injection in Chinese healthy adults. Methods A randomized, parallel, double-blind, placebo-controlled multi-day study was conducted. 24 healthy subjects were randomly divided into three dose groups of 8 patients in each group, 2 healthy subjects in each group as placebo control. The placebo subjects in three dose groups were combined into placebo group (n + 6). A group, 600000 UU B group, 900000 UU C group), 4 times a day and 4 times a day, with the interval of 3 hours each time. The first dose was given at a constant rate of 500000 U per 0. 5 h after 30 min,. The changes of vital signs electrocardiogram (ECG) indexes abnormal values and adverse events were observed before and after administration of each dose group. Results all 24 subjects completed the experiment. Among the abnormal values of laboratory examination after administration, only 5 cases in group C and placebo group had clinical significance in reducing fibrinogen to abnormal value, while the other results were normal or abnormal without clinical significance. No serious adverse reactions were observed in the trial. There were no adverse events in group A and group B. there were 2 cases of mild diarrhea associated with drugs (2 / 6) in group C. There were 3 cases of low fibrinogen (3 / 6) and 1 case of periumbilical abdominal pain (1 / 6). All adverse events were classified as grade I and were relieved by themselves without any measures taken. Conclusion Ulinastatin for injection was given multiple times in one day. The safety of ulinastatin was good in the range of 600000 U to 1.2 million U four times a day, and the subjects could tolerate it. Therefore, it is recommended that the following clinical dose should be up to 1.2 million U per time, 4 times a day.
【作者单位】：北京大学人民医院药剂科;北京大学医学部药学院;北京大学人民医院重症医学科;上海中医药大学药物临床研究中心;广东天普生化医药股份有限公司;
【基金】：国家科技部十二五重大新药创制科技重大专项基金资助项目(2012ZX09303019)
【分类号】：R969.4

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