本文選題：注射用重組人組織型纖溶酶原激活劑TNK突變體　切入點：酶聯(lián)免疫吸附實驗　出處：《中國臨床藥理學(xué)雜志》2015年09期

【摘要】：目的研究注射用重組人組織型纖溶酶原激活劑TNK突變體(rhTNK-tPA)在中國健康人體的耐受性和藥代動力學(xué)特征。方法 26例健康男性受試者分為5個劑量組: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,分別單次靜脈注射相應(yīng)劑量的rhTNK-tPA。0.2,0.4,0.6 mg·kg-1,每次20 mg組,受試者在進行耐受性試驗的同時完成藥代動力學(xué)試驗。用酶聯(lián)免疫吸附實驗(ELISA)法測定血漿rhTNK-tPA濃度。結(jié)果健康男性受試者靜脈注射rhTNK-tPA 0.2,0.4,0.6mg·kg-1和每次20 mg后,Cmax分別為(16.44±2.64),(33.38±6.55),(41.45±11.00),(28.88±6.82)ng·L-1,t1/2分別為(147.00±47.00),(197.00±40.00),(190.00±19.00)和(224.00±60.00)min,AUC0-t分別為(15.79±4.36),(36.93±9.35),(37.54±5.89),(29.35±3.63)ng·L-1·h,Vd分別為(2.97±1.04),(3.23±0.75),(4.59±1.17)和(3.71±1.18)L。與試驗藥物相關(guān)不良事件發(fā)生率為23%,程度均為輕度,未經(jīng)處理均自行消失。結(jié)論在研究劑量范圍內(nèi),rhTNK-tPA呈線性動力學(xué)特征。每次15 mg到每次20 mg作為中國人溶栓治療Ⅱ期臨床試驗的劑量可能是安全有效的劑量。
[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.
【作者單位】： 中國醫(yī)學(xué)科學(xué)院北京協(xié)和醫(yī)院阜外心血管病醫(yī)院衛(wèi)生部心血管藥物臨床研究重點實驗室;
【基金】：“重大新藥創(chuàng)制”科技重大專項基金資助項目(2012ZX09303-008-001) 2010年國家臨床重點專科建設(shè)基金資助項目
【分類號】：R969.1
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本文編號：1699899