聚乙二醇化重组人白细胞介素-6在Beagle犬体内的药物动力学
Pharmacokinetics of PEG recombinant human interleukin-6 in Beagle dog
作者：何学令;杨光;尹海林;张雪梅;
Author：
收稿日期： 年卷（期）页码：2009,24(01):-59-61
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：聚乙二醇化重组人白细胞介素-6;药物动力学
Key words：
基金项目：
中文摘要
目的研究聚乙二醇化重组人白细胞介素-6(PEG-rhIL-6)皮下注射后在Beagle犬体内的药物动力学过程,为临床应用提供药物动力学数据。方法采用同位素示踪法,碘标记PEG-rhIL-6,用液体闪烁计数仪检测放射性浓度,3p97软件判断房室模型并计算参数,检测Beagle犬皮下注射125I-PEG-rhIL-6后不同时间的血药浓度。结果Beagle犬皮下注射125I-PEG-rhIL-6后,t1/2ka为0.07～2.34h,t1/2ke为66～258h,Tmax为0.8～10.7h,体内滞留时间70～94h,AUC与剂量呈正相关。结论PEG-rhIL-6在Beagle犬体内的药物动力学过程基本符合线性药动学特征,药-时曲线符合一房室模型。经聚乙二醇(PEG)修饰的rhIL-6能明显延长rhIL-6在Beagle犬体内的生物半衰期,延长药物的有效作用时间。
参考文献
[1]Kishimoto T,Akira S,Taga T.Interleukin-6and its receptor:a paradigm for cytokines[J].Sci,1992,258(5082):593-597.
[2]Drayer AL,Sibinga CT,Blom NR,et al.Thein vitroeffects of cy-tokines on expansion and migration of megakaryocyte progenitors[J].Br J Haematol,2000,109(4):776-784.
[3]Schmitz B,Wickenhauser C,Thiele J,et al.Megakaryocyte induced fibroblast proliferation is enhanced by costimulation with IL-6/IL-3and dependent on secretory and adhesion events[J].Leuk Res,1999,23(8):723-729.
[4]尹海林,何学令,包旭,等.白细胞介素-6阻抗环磷酰胺致犬造血功能损伤的实验研究[J].生物医学工程杂志,2005,22(4):798-801.
[5]Jose VC,Thomas G,Volkcr G,et al.Plasma clearance,organ dis-tribution and target cells of interleukin-6/hepatocyte-stimula-ting factor in the rat[J].Eur J Biochem,1998,177:357-361.
[6]Rosamonde EB,Mary AF,PoulamMP,et al.Subcutaneous admin-istration of recombinant glycosylated interleukin6in patients with cancer:pharmacokinetics,pharmacodynamics and immunomodu-latory effects[J].Cytokine,2000,12(4):388-396.
[7]Harris JM,Martin NE,Modi M.Pegylation:a novel process for modifying pharmacokinetics[J].Clin Pharmacokinet,2001,40(7):539-551.
[8]Markwell MAK.A new solid-state reagent to iodinate proteins.I.conditions for the efficient labelling on antiserum[J].Anal Bio-chem,1982,125:427-432.
[9]琚志昌.生物技术药物药代动力学研究的分析方法[J].卫生研究,2002,31(2):133-135.
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