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125IrhEndostatin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：125IrhEndostatin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0.994 0。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：125IrhEndostatin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。

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 125IrhEndostatin to the rats. Plasma drug concentrationtime data were analyzed by computer fitting. Compartment model and the pharmacokinetic parameters were also established. Results: The distribution halflife time and elimination halflife 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 125IrhEndostatin. Urinary excretion was the major pathway of elimination. Conclusion: The pharmacokinetics of 125IrhEndostatin in rats basically has a linear character, and the plasma drug concentrationtime curve consists to a twocompartment model.

辽宁省科学技术厅科技基金资助（No.2001226001）