摘要
目的:比较2种生产基地来源的注射用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(TNFRIIFc)在中国健康志愿者体内药动学(pharmacokinetics,PK)特征,并评价二者的相似性。方法:24名男性健康受试者进行随机、开放、双周期两制剂交叉试验,采用经方法学验证的酶联免疫吸附分析法(ELISA)检测血清中药物浓度。Win Nonlin软件非房室模型计算PK参数,并参照生物等效性标准评价受试品(T)与参照品(R)的主要PK参数相似性。结果:本研究建立的测定人血清中TNFRII-Fc浓度的ELISA方法学指数均符合生物制品PK研究的要求。T与R的AUC0-480 h分别为(356.00±55.00)与(396.61±69.66)μg·h·mL^(-1);相对生物利用度F(T/R)为89.90%;Cmax分别为(1.70±0.50)与(1.90±0.50)μg·mL^(-1);各末端相相关PK参数相似。T的AUC0-480 h与Cmax90%置信区间分别落入R的84.10%~96.30%与78.50%~95.30%范围内。结论:研究涉及剂量下,2种产地来源的TNFRII-Fc的临床PK行为相似,可达生物等效。
Objective： To compare the clinical pharmacokinetics and evaluate the similarity of two recombinant human tumor necrosis factor receptor II-Fc fusion protein （rhTNFRII-Fc） preparations from different manufacturing facilities in Chinese healthy volunteeres.Methods： Male healthy subjects （n = 24） were recruited in a random,open,and cross-over designed trial for two preparations in two periods.The concentration of rhTNFRII-Fc inserum was measured by a validated enzymed-linked immunosorbent assay （ELISA） method.The pharmacokinetic parameter calculation,statistical analysis and the bioequivalence evaluation of the test （T） and reference （R） drug were performed using Win Nonlin software.Results： The data of the validated ELISA method met with the requirements of pharmacokinetic study.The PK data were harvested from 22 volunteers with 2 subjects withdrew from the trial.Pharmacokinetic parameters of T and R were as follows： AUC0-480 hwere （356.00 ± 55.00） and （396.61 ±69.66） μg·h·mL^（-1）,and Cmaxwere （1.70 ± 0.50） and （1.90 ± 0.50） μg·mL^（-1）,respectively.Other parameters related to elimination phase between the two preparations were similar.The relative bioavailability of the T （toR）was 89.90%.Compared to R,the value of 90% credible interval of AUC0-480 hand Cmaxof T fell into the range of84.10% ~ 96.30% and 78.50% ~ 95.30%,respectively.Conclusion： In the present study,the test and reference rhTNFRII-Fc preparations behaved comparable PK profiles in Chinese healthy volunteers,and the results of statistic analysis based on the primary PK parameters showed that two rhTNFRII-Fc preparations met the bioequivalence acceptance criteria.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2017年第19期2300-2305,共6页
Chinese Journal of New Drugs
基金
国家"重大新药创制"科技重大专项资助项目(2012ZX09301003-001-007
2015ZX09501007
2015ZX09501008)
关键词
肿瘤坏死因子受体
融合蛋白
酶联免疫吸附分析
药动学
生物等效性
tumor necrosis factor receptor
fusion protein
enzyme-linked immunosorbent assay
pharma-cokinetics
bioequivalence
