重组人血管内皮抑素在Beagle犬体内的药代动力学研究

Pharmacokinetic Research of Recombinant Human Endostatin in Beagle Dogs

研究重组人血管内皮抑素(rhEndostatin)静脉注射后在Beagle犬体内的药代动力学过程,为临床应用提供药代动力学数据。用酶联免疫吸附试验(ELISA)竞争法检测Beagle犬静脉注射rhEndostatin后不同时间的血药浓度,并将血药浓度-时间数据经计算机拟合,计算出相应参数。rhEndostatin静脉注射Beagle犬后,药物的分布半衰期平均为(0.34±0.04)h,消除半衰期为(16.5±1.6)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0.999 9。血浆清除率(CLs)均值为(0.123±0.006)l/h,高、中、低剂量CLs基本相同。rhEndostatin在Beagle犬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。rhEndostatin在Beagle犬体内药代动力学过程的研究对其进一步开发具有指导价值。

The aim of this study is to investigate the pharmacokinetics of i.v.injected recombinant human endostatin（rhEndostatin） in vivo in beagle dogs and to provide the data of pharmacokinetics for its clinical application.An enzyme linked immunosorbent assay（ELISA） was used to measure the plasma drug concentration of rhEndostatin in different periods of time after i.v.injection in the dogs.The obtained plasma drug concentration-time data were analyzed by computer fitting and then the compartment model and the pharmacokinetic parameters were also established.The distribution half-life time and elimination half-life time of rhEndostatin in the rhEndostatin injected dogs were（0.34±0.04） h and（16.5±1.6） h,respectively.The AUC were positively correlated with the dosages（r=0.999 9） and the mean CLs was（0.123±0.006） L/h.The numeric CLs were basically the same among the high,middle or low dosages.The pharmacokinetics of rhEndostatin in the dogs after i.v.injection was in correspondence with two-compartment model.These findings indicate that rhEndostatin has a potential therapeutic use in tumor therapy.