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刊物信息

期刊名称:药物分析杂志
主管单位:中国科学技术协会
主办单位:中国药学会
承办:中国食品药品检定研究院
主编:金少鸿
地址:北京天坛西里2号
邮政编码:100050
电话:010-67012819,67058427
电子邮箱:ywfx@nicpbp.org.cn
国际标准刊号:ISSN 0254-1793
国内统一刊号:CN 11-2224/R
邮发代号:2-237
 

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重组人源化抗人IL-6R单克隆抗体BAT-1806注射液单次给药药代动力学研究

Pharmacokinetics of recombinant humanized anti-human interleukin 6 receptor monoclonal antibody BAT-1806 injection after single administration

作者(英文):
分类号:R917
出版年·卷·期(页码):2018,38 (10):1775-1780
DOI: 10.16155/j.0254-1793.2017.01.01
-----摘要:-------------------------------------------------------------------------------------------

目的:研究食蟹猴单次静脉注射BAT-1806的药代动力学特征,并与托珠单抗(tocilizumab,TOC)进行一致性对比。方法:24只食蟹猴按体质量随机分为4组,雌雄各半,分别单次给予不同剂量(10,30mg·kg-1)的BAT-1806注射液和TOC注射液,在不同时间点采血分离血浆,用ELISA法测定血浆中药物浓度,根据非房室统计模型矩模型用WinNolin药代软件对测定结果进行曲线拟合并计算药代动力学参数,比较BAT-1806和TOC的药代动力学参数和评价其生物等效性。结果:食蟹猴单次静脉注射10 mg·kg-1和30 mg·kg-1的BAT-1806,Tmax分别为(0.58±0.38)h和(0.25±0.42)h,T1/2分别为(81.6±54.5)h和(105.7±30.2)h,Cmax分别为(202 415±39 064)ng·mL-1和(613 161±133 207)ng·mL-1,AUC(0-t分别为(17 614 098±3 716 972)h·ng·mL-1和(55 333 524±16 351 767)h·ng·mL-1Vd分别为(66.6±37.5)mL·kg-1和(84.3±21.8)mL·kg-1,Cl分别为(0.58±0.13)mL·h-1·kg-1和(0.58±0.16)mL·h-1·kg-1,MRT分别为(107.8±15.5)h和(177.2±28.6)h。BAT-1806在食蟹猴体内的药代动力学特征不存在性别差异。BAT-1806与TOC的主要药代动力学参数无显著性差异。在10 mg·kg-1剂量下,BAT-1806与TOC的Cmax和AUC(0-t比率分别为0.98和1.05;在30 mg·kg-1剂量下,BAT-1806和TOC的Cmax和AUC(0-t比率分别为0.98和0.92。结论:BAT-1806和TOC在食蟹猴体内的药代动力学特征具有一致性且生物等效。

-----英文摘要:---------------------------------------------------------------------------------------

Objective:To study the pharmacokinetics of BAT-1806 after a single intravenous injection in cynomolgus monkeys, and carry out conformance comparison with TOC.Methods:Twenty four cynaomolgus monkeys were randomly divided into four groups according to their body mass, half female and half male.They were given single doses of 10 and 30 mg·kg-1 of BAT1806 injection or TOC injection.Blood samples were collected at different time points and the plasma concentrations were determined by ELISA.The data obtained were subjected to noncompartment pharmacokinetic analysis using WinNonlin software.Pharmacokinetic parameters were compared and the bioequivalence between BAT1806 and TOC was evaluated.Results:After given a single intravenous injection of BAT-1806 with 10 mg·kg-1 or 30 mg·kg-1, Tmax was(0.58±0.38) h and(0.25±0.42) h, T1/2 was(81.6±54.5) h and(105.7±30.2) h, Cmax was(202 415±39 064) ng·mL-1 and(613 161±133 207) ng·mL-1, AUC(0-t) was(17 614 098±3 716 972) h·ng·mL-1 and(55 333 524±16 351 767) h·ng·mL-1, Vd was(66.6±37.5) mL·kg-1 and(84.3±21.8) mL·kg-1, Cl was(0.58±0.13) mL·h-1·kg-1 and(0.58±0.16) mL·h-1·kg-1, MRT was(107.8±15.5) h and(177.2±28.6) h, respectively.There was no gender difference in the pharmacokinetic characteristics of BAT-1806 in cynomolgus monkeys.There was no significant difference in the main pharmacokinetic parameters between BAT-1806 and TOC, indicating that the pharmacokinetic characteristics of the two drugs are consistent.The Cmax and AUC(0-t) ratios of the 10 mg·kg-1 BAT-1806 and TOC were 0.98 and 1.05, respectively, and the Cmax and AUC(0-t) ratios of 30 mg·kg-1 BAT-1806 and TOC were 0.98 and 0.92.Conclusion:The pharmacokinetic characteristics of the BAT1806 or TOC are conformable and bioequivalent.

-----参考文献:---------------------------------------------------------------------------------------
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