重组人组织型纤溶酶原激活剂TNK突变体在中国健康人体的耐受性及药代动力学研究

发布时间：2018-04-02 10:09

  本文选题：注射用重组人组织型纤溶酶原激活剂TNK突变体　切入点：酶联免疫吸附实验　出处：《中国临床药理学杂志》2015年09期

【摘要】：目的研究注射用重组人组织型纤溶酶原激活剂TNK突变体(rhTNK-tPA)在中国健康人体的耐受性和药代动力学特征。方法 26例健康男性受试者分为5个剂量组:0.1 mg·kg-12例,0.2 mg·kg-18例,0.4mg·kg-18例,0.6 mg·kg-12例,每次20 mg 6例,分别单次静脉注射相应剂量的rhTNK-tPA。0.2,0.4,0.6 mg·kg-1,每次20 mg组,受试者在进行耐受性试验的同时完成药代动力学试验。用酶联免疫吸附实验(ELISA)法测定血浆rhTNK-tPA浓度。结果健康男性受试者静脉注射rhTNK-tPA 0.2,0.4,0.6mg·kg-1和每次20 mg后,Cmax分别为(16.44±2.64),(33.38±6.55),(41.45±11.00),(28.88±6.82)ng·L-1,t1/2分别为(147.00±47.00),(197.00±40.00),(190.00±19.00)和(224.00±60.00)min,AUC0-t分别为(15.79±4.36),(36.93±9.35),(37.54±5.89),(29.35±3.63)ng·L-1·h,Vd分别为(2.97±1.04),(3.23±0.75),(4.59±1.17)和(3.71±1.18)L。与试验药物相关不良事件发生率为23%,程度均为轻度,未经处理均自行消失。结论在研究剂量范围内,rhTNK-tPA呈线性动力学特征。每次15 mg到每次20 mg作为中国人溶栓治疗Ⅱ期临床试验的剂量可能是安全有效的剂量。
[Abstract]:Objective to study the tolerance and pharmacokinetics of recombinant human tissue plasminogen activator (TNK) mutant rhTNK-tPA in Chinese healthy volunteers.Methods 26 healthy male subjects were divided into 5 groups: 0. 1 mg kg-12, 0. 2 mg kg-18, 0. 4 mg kg-18 and 0. 6 mg kg-12, 20 mg / time, respectively. The corresponding dose of rhTNK-tPA. 0.42 0.40.40 mg kg-1 was injected intravenously, 20 mg / time, respectively.The subjects completed the pharmacokinetic test at the same time as the tolerance test.Plasma rhTNK-tPA concentration was determined by Elisa.The incidence of drug-related adverse events was 23, mild and disappeared without treatment.Conclusion rhTNK-tPA shows linear kinetic characteristics in the range of study dose.The dosage of 15 mg to 20 mg each time may be a safe and effective dose for stage II clinical trial of Chinese thrombolytic therapy.
【作者单位】： 中国医学科学院北京协和医院阜外心血管病医院卫生部心血管药物临床研究重点实验室;
【基金】：“重大新药创制”科技重大专项基金资助项目(2012ZX09303-008-001) 2010年国家临床重点专科建设基金资助项目
【分类号】：R969.1
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本文编号：1699899