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目的:研究国产重组人血小板生成因子注射液在健康志愿者体内的药动学特征,为II期临床试验提供合理的用药方案,以及新药的审批提供理论依据.方法:27名健康志愿者随机分为0.5,1.0和2.0μg/kg三个剂量组,单次皮下注射重组人血小板生成因子注射液,用ELISA法测定人血清中rhTPO浓度.结果:药代动力学参数如下:T1/2ke分别为(46.74±6.36),(48.53±2.29)和(51.88±3.34)h;T1/2ka分别为(2.17±0.53),(2.64±0.53)和(2.84±0.62)h;Tpeak分别为(10.00±1.51),(10.22±1.20)和(10.00±1.00)h;ρmax分别为(312.29±61.65),(465.14±46.94)和(811.34±106.73)ng/L;AUC(0-216h)分别为(17269.92±4470.23),(29710.56±3890.28)和(53358.41±5608.01)ng/L·h.结论:当以0.5～2.0μg/kg单次皮下注射重组人血小板生成因子注射液时,其在正常人体内表现为线性药动学特征,消除半衰期较长.推荐II期临床给药剂量为皮下注射1.0μg/kg,1次/d,连续7d.
Objective: To study the pharmacokinetic characteristics of domestic recombinant human thrombopoietin injection in healthy volunteers, to provide a reasonable drug regimen for Phase II clinical trials and to provide a theoretical basis for the approval of new drugs.Methods: 27 healthy volunteers were randomized 0.5, 1.0 and 2.0μg / kg three doses, a single subcutaneous injection of recombinant human platelet factor injection, rhTPO concentration in human serum by ELISA method.Results: The pharmacokinetic parameters are as follows: T1 / 2ke were (46.74 ± 6.36), (48.53 ± 2.29) and (51.88 ± 3.34) h, respectively. The T 1/2 values were (2.17 ± 0.53), (2.64 ± 0.53) and (10.22 ± 1.20) and (10.00 ± 1.00) h respectively; ρmax were (312.29 ± 61.65) and (465.14 ± 46.94) and (811.34 ± 106.73) ng / L, respectively; AUC (0-216h) were (17269.92 ± 4470.23), (29710.56 ± 3890.28) and (53358.41 ± 5608.01) ng / L · h respectively.CONCLUSIONS: When injected subcutaneously with 0.5-2.0 μg / kg recombinant human thrombopoietin injection, Linear pharmacokinetic characteristics, elimination half-life longer recommended II clinical dose of subcutaneous injection of 1.0μg / kg, 1 / d, continuous 7d.