2种重组人Ⅱ型肿瘤坏死因子受体-Fc融合蛋白的临床生物等效性评价

发布时间：2018-05-03 15:17

本文选题：肿瘤坏死因子受体 + 融合蛋白　；参考：《中国新药杂志》2017年19期

【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。
[Abstract]:Objective: to compare the pharmacokinetic characteristics of recombinant human tumor necrosis factor receptor-antibody fusion protein (TNFRIIFc) from two production bases in Chinese healthy volunteers and to evaluate their similarity. Methods Twenty four healthy male subjects were randomly divided into two groups: open, double-cycle cross-test. Elisa was used to detect the concentration of drugs in serum. The non-atrioventricular model of win Nonlin software was used to calculate the competition parameters. The similarity of the main competitive parameters between TX and R) was evaluated with reference to the bioequivalence criteria. Results: the ELISA methodological indices for the determination of TNFRII-Fc concentration in human serum were all in line with the requirements of the competition study of biological products. The AUC0-480 h of T and R were 356.00 卤55.00 and 396.61 卤69.66 渭 g / h, respectively, and the relative bioavailability of FN / R was 89.90 卤0.50 渭 g / mL and 1.90 卤0.50 渭 g / mL, respectively, and the relative bioavailability was 89.90 卤0.50 and 1.90 卤0.50 渭 g / mL respectively, and the relative bioavailability was 89.90 卤0.50 and 1.90 卤0.50 渭 g / mL respectively. The AUC0-480 h and Cmax90% confidence intervals with similar competition parameters fall into the range of 96.30% and 95.30% of R, respectively. Conclusion: the clinical competitive behaviors of TNFRII-Fc from two sources were similar and bioequivalent.
【作者单位】：军事医学科学院放射与辐射医学研究所药理毒理研究室;军科正源(北京)药物研究有限责任公司;解放军第306医院急诊科;浙江海正药业股份有限公司;
【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)
【分类号】：R969.1

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