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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 pharmacokinetics (PK) characteristics of recombinant human type II TNFRI-Fc (TNFRIFc) injected from two production sites in healthy volunteers in China and to evaluate their comparability . Methods: Twenty-four male healthy subjects were randomized, open and double-cycle crossover test. Serum drug concentrations were determined by a methodologically validated enzyme-linked immunosorbent assay (ELISA). Win Nonlin software non-compartmental model was used to calculate the PK parameters and the bioequivalence criteria were used to evaluate the similarity of the major PK parameters between the test sample (T) and the reference sample (R). Results: The ELISA methodological index established in this study to determine the concentration of TNFRII-Fc in human serum all met the requirements of the PK study of biological products. The AUC0-480 h of T and R were (356.00 ± 55.00) and (396.61 ± 69.66) μg · h · mL -1, respectively. The relative bioavailability F (T / R) was 89.90% 1.70 ± 0.50) and (1.90 ± 0.50) μg · mL -1, respectively. The PK parameters of each terminal phase were similar. The AUC0-480 h of T and the 90% confidence interval of Cmax fall within the range of 84.10% -96.30% and 78.50% -95.30% of R, respectively. CONCLUSIONS: The clinical PK behavior of the two TNFRII-Fc-producing sources at the dose-related studies was similar and bioequivalent.