中国临床药理学杂志2018，Vol.34Issue(3)：312-315,326,5.DOI:10.13699/j.cnki.1001-6821.2018.03.037
注射用重组人肿瘤坏死因子受体突变体-Fc融合蛋白对中国健康志愿者血浆中肿瘤坏死因子-α浓度水平的影响
Effects of recombinant fusion protein of human tumor necrosis factor receptor mutant and Fc fragment for injection on the plasma concentration of tumor necrosis factor-α in Chinese healthy volunteers
王艺瞳 1栗占国 2宋海峰 3方翼 4李艳 1刘畅 1王炜 5王茜 1董立厚 6陈适 1臧彦楠 4谢振伟3
作者信息
- 1. 北京大学人民医院药剂科,北京 100044
- 2. 北京大学医学部药学院,北京 100191
- 3. 北京大学人民医院风湿免疫科,北京 100044
- 4. 军事医学科学院放射与辐射医学研究所,北京 100850
- 5. 山西医科大学药学院,太原 030001
- 6. 上海复旦张江生物医药股份有限公司医学部,上海 201210
- 折叠
摘要
Abstract
Objective To access the effects of different doses of recombinant fusion protein of human tumor necrosis factor receptor mutant and Fc fragment [rhTNFR(m):Fc] after a single subcutaneous injection on the plasma concentration of tumor necrosis factor-α (TNF-or) in Chinese healthy volunteers.Methods A total of 56 healthy Chinese volunteers were randomly divided into 6 groups to receive a single injection of 10,20,35,65,75 mg of rhTNFR(m):Fc.The plasma concentrations of TNF-α and total TNF-α were determined at 1 h pre-dose and at 4,48,96,168,216,264,312,384,480 h post-dose.Results After administration of rhTNFR(m):Fc at 0-264 h,the plasma concentrations of free TNF-α and total TNF-α increased significantly in the each group.At 264-480 h post-dose,the concentration of them began to decrease,and at 480 h the concentration of free TNF-α almostly decreased to normal levels.In the dose range of 10-75 mg,the exposure of free TNF-α and total TNF-α (Cmax) had no significant correlation with the dose of rhTNFR (m):Fc.Conclusion After giving the single dose of rhTNFR (m):Fc,there was an increase of free and total TNF-α plasma concentration in Chinese healthy volunteers.As a result,the plasma concentration of free and total TNF-α may not be a suitable pharmacodynamic evaluation index.关键词
重组人肿瘤坏死因子受体突变体-Fc融合蛋白/肿瘤坏死因子-α/依那西普Key words
recombinant fusion protein of human tumor necrosis factor receptor mutant and Fc fragment/tumor necrosis factor-α/etanercept分类
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王艺瞳,栗占国,宋海峰,方翼,李艳,刘畅,王炜,王茜,董立厚,陈适,臧彦楠,谢振伟..注射用重组人肿瘤坏死因子受体突变体-Fc融合蛋白对中国健康志愿者血浆中肿瘤坏死因子-α浓度水平的影响[J].中国临床药理学杂志,2018,34(3):312-315,326,5.
