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目的:研究重组人单克隆抗体CTLA4Ig经静脉单次给药后在猕猴体内的药动学过程,评价剂量与药动学参数之间的关系。方法:9只猕猴分为3组,3组分别单次给药(50,10和2 mg.kg-1),按不同时间点采血分离血清,ELISA法测定血清中CTLA4Ig的浓度,根据非房室统计矩模型用WinNolin药代软件进行曲线拟合并计算药动学参数。结果:猕猴分别静脉单次注射高、中、低(50,10,2 mg.kg-1)CTLA4Ig后,对应的AUC2-inf与剂量呈现线性正相关性,剂量之比为25∶5∶1,对应的AUC比值为24.99∶4.73∶1;三个剂量的t1/2和CLs相近,说明在本实验的剂量范围内剂量的变化在猕猴体内对CTLA4Ig的t1/2和CLs没有影响。结论:在本实验的剂量范围内,CTLA4Ig在猕猴体内符合线性药动学特点。
OBJECTIVE: To study the pharmacokinetics of recombinant human monoclonal antibody CTLA4Ig in rhesus monkeys after single intravenous administration, and to evaluate the relationship between dosage and pharmacokinetic parameters. Methods: Nine cynomolgus monkeys were divided into three groups. The three groups were given single administration (50, 10 and 2 mg.kg-1) respectively. Serum was separated by blood sampling at different time points. The concentration of CTLA4Ig in serum was determined by ELISA. Pharmacokinetic parameters were calculated by curve fitting with WinNolin pharmacokinetics in the statistical moment model. Results: After a single injection of CTLA4Ig with high, medium and low doses (50,10,2 mg.kg-1) into the cynomolgus monkeys, the corresponding AUC2-inf showed a positive linear correlation with the dose, with a dose ratio of 25: 5: 1 , Corresponding to an AUC ratio of 24.99: 4.73: 1; t1 / 2 at three doses was similar to CLs, indicating that dose changes in the dose range of this experiment had no effect on t 1/2 and CLs of CTLA4Ig in rhesus monkeys. CONCLUSIONS: In the dose range of this experiment, CTLA4Ig is linearly pharmacokinetic in rhesus monkeys.