摘要
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.
AIM： To study the pharmacokinetics after a single subcutaneous injection of China-made recombinant human thrombopoietin （ rhTPO, a product of Zhongxinguojian Pharmaceutical Co Ltd）in healthy volunteers. METHODS：Twentyseven healthy volunteers were randomized to 3 groups. The volunteers in the 3 groups received a single injection of rhTPO in a dosage of 0.5, 1.0 and 2.0 μg/kg respectively. Blood samples were collected serially before and after the medication. The rhTPO concentrations in serum were determined by ELISA. RESULTS： The pharmacokinetic parameters obtained were： T1/2ke occurred at （46.74 ±6.36）, （48.53 ±2.29） and （51.88 ±3.34） h; T±/2ka were（2.17±0.53）, （2.64±0.53） and （2.84±0.62） h; Tpeakwere （10.00±1.51）, （10.22±1.20） and （10.00 ±1.00）h;fmax were （312.29 ±61.65）, （465. 14 ±46.94） and（811.34 ± 106.73） ng/L; AUC（0-216h） were （17269.92±4470. 23）, （29710.56± 3890. 28） and （53358.41±5608.01） ng/L. h. CONCLUSION： When administrated subcutaneously in human within the dosage of 0.5 - 2. 0μg/kg, rhTPO has the characteristics of linear pharmacokinetics, with longer half-life elimination. For clinical application in phase Ⅱ trial, the recommended daily dosage is 1.0μg/kg, subcutaneous injection for 7 d.
出处
《第四军医大学学报》
北大核心
2005年第15期1427-1430,共4页
Journal of the Fourth Military Medical University
