重组人血管内皮细胞抑制因子在大鼠体内的组织分布及药代动力学  

Distribution and pharmacokinetics of recombinant human endostatin in rats

作　　者：刘江秋[1] 凌磊[2] 刘延秋[3] 李杰英[2] 赵炜[2] 朱荔清[2] 朱晓红[2] 吴彩中[2] 徐璐[2] 李忠义[1] 

机构地区：[1]沈阳军区联勤部疾病预防控制中心,沈阳110034 [2]中国人民解放军第202医院,沈阳110003 [3]济南军区联勤部疾病预防控制中心,济南250014

出　　处：《中国肿瘤生物治疗杂志》2007年第2期158-162,共5页Chinese Journal of Cancer Biotherapy

基　　金：辽宁省科学技术厅科技基金资助(No.2001226001)

摘　　要：目的:研究重组人血管内皮细胞抑制因子(rhEndostatin)静脉注射后在Wistar大鼠体内的药代动力学过程,为其临床应用提供药代动力学数据。方法:应用放射性核素示踪技术结合三氯醋酸沉淀法(TCA沉淀法),对125I-rhEndostatin静脉注射大鼠后不同时间、不同组织内的核素分布量进行测定,并将血药浓度-时间数据经计算机拟合,计算出相应参数。结果:125I-rhEndostatin静脉注射大鼠后,药物的分布半衰期平均为(0.154±0.024)h,消除半衰期为(4.03±0.58)h。血药浓度-时间曲线下面积(AUC)与剂量呈正相关,相关系数为0.9940。血浆清除率(CLs)均值为(0.165±0.024)L/h,高、中、低剂量CLs基本相同。该药在大鼠肝、肺、脾、胃、甲状腺中有较高聚集,主要经肾脏排泄。结论:125I-rhEndostatin在大鼠体内的药代动学过程基本符合线性药动学特征,血药浓度-时间曲线符合二房室模型。Objective： To investigate the in vivo pharmacokinetics of recombinant human Endostatin （rhEndostatin） in Wistar rats after i.v. injection, so as to provide pharmacokinetic data for clinical application. Methods：Radioactive isotopic （^125I） tracing combined with trichloroacetic acid （TCA） precipitation was used to measure the residual isotope in different tissues at different time points after i. v. injection of ^125I-rhEndostatin to the rats. Plasma drug concentration-time data were analyzed by computer fitting. Compartment model and the pharmacokinetic parameters were also established. Results： The distribution half-life time and elimination half-life time of rhEndostatin in rats were （0. 154 ＋ 0. 024） h and （4.03 ＋0.58） h, respectively. The AUC were positively correlated with dosages of rhEndostatin （r = 0. 9940）. The mean of CLs value was （0. 165 ＋ 0. 024）L/h; the CLs values for high, middle or low dosages were basically the same. The liver, lung, spleen, stomach and thyroid were the major organs for deposition of ^125I-rhEndostatin. Urinary excretion was the major pathway of elimination. Conclusion： The pharmacokinetics of ^125 I-rhEndostatin in rats basically has a linear character, and the plasma drug concentration-time curve consists to a two-compartment model.

关 键 词：血管内皮细胞抑制因子 ^125I标记 组织分布 药代动力学 

分 类 号：R734.2[医药卫生—肿瘤]