学术
猕猴体内白蛋白融合干扰素α-2b（HSA-IFNα-2b）的药代动力学研究
邢文会[1] 杨萍[2] 汪海霞[2] 杨健良[2]
[1]河南教育学院人口与生命科学系,河南郑州450014 [2]浙江德清安平生物制药有限公司,浙江湖州313200
摘 要:
目的研究白蛋白融合干扰素α-2b（HSA-IFNα-2b）在猕猴体内的药代动力学。方法按照50μg·kg^-1v、50μg·kg^-1c和300μg·kg^-1c3种剂量组给猕猴注射HSA-IFNα-2b,分别在14个时间点采血,用ELISA方法测定血药浓度,计算药代动力学参数。结果3组受试猕猴均能在336h以前的各时间点测到HSA-IFNα-2b药物。一房室模型（weight=1/C2）分析药物浓度-时间曲线显示：50μg·kg^-1v、50μg·kg^-1c和300μg·kg^-1c3个剂量组的分布容积分别为67、71和63ml·kg^-1。HSA-IFNα-2b皮下注射吸收相对缓慢,单剂量50μg·kg^-1c的吸收半衰期约为19h,消除半衰期为53h,清除率为0.92ml·h^-1·kg^-1,生物利用度达73%。结论HSA-IFNα-2b猕猴体内研究表明其药代动力学优于非融合干扰素,提示使用HSA-IFNα-2b可以减少用药次数,并有可能提高疗效。[著者文摘]
文章出处:
《中国药理学通报》-2007年23卷9期 -1156-1160页
栏目信息:
文献标识码:
A
文章编号:
1001-1978（2007）09-1156-05
Pharmacokinetics study of albumin-interferon α-2b fusion protein （HSA-IFNα-2b） in Rhesus Monkey
XING Wen-hui, YANG Ping, WANG Hai-xia ,YANG Jian-liang （1. Dept of Population and Life Science, Henan Institute of Education ,Zhengzhou 450014, China; 2. Zhejiang Deqing Anping Bio-pharma Co,Huzhou Zhejiang 313200 ,China）
Abstract:
Aim To investigate the pharmacokinetics of albumin-interferon α-2b fusion protein（HSA-IFNα-2b） in Rhesus monkeys.Methods Three groups of monkeys were administrated by single injection of HSA-IFNα-2b at 50 μg·kg^-1v,50 μg·kg^-1c and 300 μg·kg^-1c,respectively.Blood samples were taken at 14 different time points from each animal.ELISA was employed to determine the drug concentrations in plasma for all samples.Results Drug was detectable in all of the treated monkeys up to 336 hours after administration.One-compartment model analysis showed that distribution volume was 71 ml·kg^-1in 50 μg·kg^-1v group,67 ml·kg^-1in 50 μg·kg^-1c group,and 63 ml·kg^-1in 300 μg·kg^-1 group,respectively.The absorption of HSA-IFNα-2b was relatively slow when given by subcutaneous injection.After 50 μg·kg^-1c,the absorption half-life was 19h and elimination half-life was 53h,the bioavailability（F） was approximately 73%,and the apparent clearance（clearance divided by bioavailability,CL/F） was 0.92 ml·h^-1·kg^-1onclusion The result showed that HSA-IFNα-2b may offer the benefits of less frequent dosing and a potentially improved efficacy profile compared with non-albumin fused IFN-alpha.[著者文摘]
Key words:
albumin-interferon α-2b fusion protein（HSA-IFNα-2b）;pharmacokinetics;ELISA（enzyme-linked immunosorbant assay）;Rhesus Monkey
基金资助:
浙江省科技厅重点科研项目（No 2006C3004）
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