Bioequivalence evaluation of two rhTNFR Ⅱ-Fc preparations from different manufacturing facilities in Chinese healthy volunteers
DONG Li-hou
HAN Min
FAN Xiao-dong
XIE Xin-yao
WANG Bian-zhen
CHEN Fang
ZOU Jia
FU Jie
CHEN Fang-qing
OU Lun
SONG Hai-feng
Abstract：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 in serum 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 WinNonlin 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 h were (356.00 ± 55.00) and (396.61 ± 69.66) μg· h· mL-t,and Cmax were (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 (to R) was 89.90％.Compared to R,the value of 90％ credible interval of AUC0-480 h and Cmax of T fell into the range of 84.10％ ～ 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.
Keywords：tumor necrosis factor receptorfusion proteinenzyme-linked immunosorbent assaypharmacokineticsbioequivalence
Publication Date：2017-01-01
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：6( 2300-2305 )