本文選題：腫瘤壞死因子受體 + 融合蛋白��； 參考：《中國新藥雜志》2017年19期

【摘要】：目的:比較2種生產(chǎn)基地來源的注射用重組人Ⅱ型腫瘤壞死因子受體-抗體融合蛋白(TNFRIIFc)在中國健康志愿者體內(nèi)藥動學(pharmacokinetics,PK)特征,并評價二者的相似性。方法:24名男性健康受試者進行隨機、開放、雙周期兩制劑交叉試驗,采用經(jīng)方法學驗證的酶聯(lián)免疫吸附分析法(ELISA)檢測血清中藥物濃度。Win Nonlin軟件非房室模型計算PK參數(shù),并參照生物等效性標準評價受試品(T)與參照品(R)的主要PK參數(shù)相似性。結(jié)果:本研究建立的測定人血清中TNFRII-Fc濃度的ELISA方法學指數(shù)均符合生物制品PK研究的要求。T與R的AUC0-480 h分別為(356.00±55.00)與(396.61±69.66)μg·h·mL~(-1);相對生物利用度F(T/R)為89.90%;Cmax分別為(1.70±0.50)與(1.90±0.50)μg·mL~(-1);各末端相相關(guān)PK參數(shù)相似。T的AUC0-480 h與Cmax90%置信區(qū)間分別落入R的84.10%~96.30%與78.50%~95.30%范圍內(nèi)。結(jié)論:研究涉及劑量下,2種產(chǎn)地來源的TNFRII-Fc的臨床PK行為相似,可達生物等效。
[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 鹵55.00 and 396.61 鹵69.66 渭 g / h, respectively, and the relative bioavailability of FN / R was 89.90 鹵0.50 渭 g / mL and 1.90 鹵0.50 渭 g / mL, respectively, and the relative bioavailability was 89.90 鹵0.50 and 1.90 鹵0.50 渭 g / mL respectively, and the relative bioavailability was 89.90 鹵0.50 and 1.90 鹵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.
【作者單位】： 軍事醫(yī)學科學院放射與輻射醫(yī)學研究所藥理毒理研究室;軍科正源(北京)藥物研究有限責任公司;解放軍第306醫(yī)院急診科;浙江海正藥業(yè)股份有限公司;
【基金】：國家“重大新藥創(chuàng)制”科技重大專項資助項目(2012ZX09301003-001-007,2015ZX09501007,2015ZX09501008)
【分類號】：R969.1

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