CAJ | 학술논문

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。
목적：탐색주사용오사타정재중국건강성년수시자중단일다차급약적안전성、내수성。방법채용수궤、평행、쌍맹、안위제대조적1천다차급약연구설계，장24례건강수시자수궤분위A、B、C 3개제량조，매조8례，기중매조2명건강수시자작안위제대조，3개제량조적안위제수시자합병위안위제조（n＝6）。A조매차급약60만U， B조매차급약90만U，C조매차급약120만U，3조균1천4차，매량차급약간격위3 h。수제급약균속완만추주30 min，기후적3차급약안매0．5 h적주50만U적속도균속정맥적주。관찰각제량조적수시자재급약전후적생명체정변화、심전도검사결과、실험실각검사항목지표적변화이급이상치화불량사건。결과24례수시자균완성시험。급약후실험실검사이상치중，부C조화안위제조적5례섬유단백원강저위이상유림상의의，기타검사결과균위정상혹이상무림상의의。시험중，미견엄중불량반응。기중，A조화B조미발생임하불량사건。C조출현2례차여약물가능상관적경도복사（2／6）、3례차여약물가능무관적섬유단백원편저（3／6）화1례차여약물가능무관적제주복통（1／6）。소유불량사건균위Ⅰ급，병차균재미채취임하조시적정황하자행완해。결론주사용오사타정1천다차급약，재매천4차，매차60만U도120만U적급약범위내，안전성교호，수시자균가내수。인차，건의후속림상사용제량최고가체도매차120만U，매천4차。
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.