论文部分内容阅读
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 study the pharmacokinetics of rhEndostatin in Wistar rats after intravenous injection, and to provide pharmacokinetic data for its clinical application. Methods: Radionuclide tracer technique combined with trichloroacetic acid precipitation (TCA precipitation method) was used to measure the amount of radionuclide in different tissues after 125I-rhEndostatin was intravenously injected into rats. The plasma concentration- Time data by computer fit, calculate the corresponding parameters. Results: After intravenous injection of 125I-rhEndostatin, the half-life of drug distribution was (0.154 ± 0.024) h and the elimination half-life was (4.03 ± 0.58) h. The area under the plasma concentration-time curve (AUC) was positively correlated with the dose, with a correlation coefficient of 0.9940. The average plasma clearance (CLs) was (0.165 ± 0.024) L / h, high, medium and low dose CLs were basically the same. The drug in rat liver, lung, spleen, stomach, thyroid in a higher aggregation, the main excretion by the kidneys. Conclusion: The pharmacokinetics of 125I-rhEndostatin in rats is basically consistent with the linear pharmacokinetic characteristics, and the plasma concentration-time curve conforms to the two-compartment model.