乌司他丁在中国健康成年受试者中的耐受性研究  

Tolerance study of ulinastatin injection in Chinese healthy volunteers

作　　者：刘阳[1,2] 王茜[1] 赵慧颖[3] 姜道利[1] 王艳[1] 李佳朋 韦忠娜[1] 安友仲[3] 戎练晨 许羚[5] 赵立波[1] 方翼[1] 

机构地区：[1]北京大学人民医院药剂科,北京100044 [2]北京大学医学部药学院,北京100191 [3]北京大学人民医院重症医学科,北京100044 [4]上海中医药大学药物临床研究中心,上海200021 [5]广东天普生化医药股份有限公司,广州510520

出　　处：《中国临床药理学杂志》2015年第21期2111-2113,共3页The Chinese Journal of Clinical Pharmacology

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)

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。Objective To evaluate the safety and tolerance of multi-dose of ulinastatin （ UTI ） injection in Chinese healthy volunteers. Methods This is a parallel, randomized, double -blind, placebo -controlled, multi-dose study, and 24 health volunteers were randomized into A, B, C three dose groups.In each group, 2 subjects were adminis-trated with placebo and 6 subjects with UTI.Each health volunteer re-ceived four doses a day, with interval period of 3 h.The health volun-teers in group A, B and C were administrated 6 ×105 , 9 ×105 and 12 ×105 U UTI at each dose, respectively.Each subject received the first dose of UTI by intravenous infusion over 30 minutes at a stable rate using an infusion pump, and the following three doses via intravenously drip at a rate of 5 ×105 U/0.5 h.Adverse events （ AEs） , vital signs and laboratory tests throughout the study were used to assess the safety and tolerance.Results All the 24 healthy volunteers finished the study. After administration of UTI, 5 cases of fibrinogen（FIB） with clinical sig-nificance occurred in C group and placebo group, other test results were normal or abnormal with no clinical significance.During the trail, no serious AEs were observed.No AEs occurred in the group A and group B.Only 2 cases of slight and mild diarrhea, probably related to the drug, and 1 case of periumbilical abdominal pain, probably unrelated to the drug, were observed in group C （ except the placebo group）;3 and 2 cases of FIB, probably unrelated to the drug, were observed in group C and placebo group, respectively.All AEs were of grade I according to the common terminology criteria for adverse events （ CTCAE） version 4.0 and required no medical intervention.Conclusion Multi-dose （ qid） ranged from 6 ×105 U to 12 ×105 U of UTI in Chinese healthy volunteers was safe and well tolerant.It is recommended that dose up to 12 ×105 U （ qid） may be tested for the follow-up clinical trials.

关 键 词：乌司他丁 中国健康成年受试者 单日多次给药 安全性 耐受性 

分 类 号：R977.3[医药卫生—药品] R969.1[医药卫生—药学]