聚乙二醇化重组新型人白细胞介素-6的药代动力学研究

以双相氯胺-T法标记,应用^125I示踪技术对新研制的聚乙二醇化重组人白细胞介素-6（PEG-rhIL-6）的药代动力学进行研究,试验选取不分雌雄30只SD大鼠,随机分成6个组,1～3组皮下注射给药,剂量分别为40μg/kg（高剂量组）,20μg/kg（中剂量组）和3μg/kg（低剂量组）,4～6组静脉注射给药（剂量同...

PHARMACOKINETICS OF PEGYLATED RECOMBINAN NEW HUMAN INTERLEUKIN-6(PEG-rhIL-6)

In this study, the newly developed Pegylated recombinan human Interleukin-6 (PEG-rhIL-6) was investigated. With 125I labeled PEG-rhIL-6 by two-phase chloramine-T method. Thirty of the SD rats were randomly divided into 6 groups(group 1, 2, 3, 4,5 and 6,respectively), with 5 animals (3 males and 2 females) each group. Group 1,2, and 3 were injected subcutaneously with125I-PEG-rhIL-6 at the dose of 40, 20 and 3μg/kg, respectively. Group 4,5, and 6 were injected intravenously with125I-PEG-rhIL-6 with the same dose level, respectively. Blood samples were collected at different time intervals after injection. The plasma concentration(ng/ml)of125I-PEG-rhIL-6 were determined by125I isotope tracing method and then assessed with 3P87 software to obtain the pharmacokinetic parameters. Results clearly showed that 1/2ke(20.41, 21.53, 19.77)and t1/2ka(10.44, 11.26, 11.37)of group1-3 are higher number than t1/2β(17.54, 18.78, 17.81)and t1/2α(1.93, 1.60, 1.78)of grou4-6,The pharmacological activity of125I-PEG-rhIL-6 maintain longer time by subcutaneous injection; The pharmacokinetic of V/Fc after sc(694.96ml/kg)is higher than those after iv(115.26ml/kg), which showed that the excretion speed of125I-PEG-rhIL-6 given by sc was slowly. The above results obtained indicated that the pharmacokinetic characteristics of125I-PEG-rhIL-6 would provide important information for clinical application and the subcutaneous injection is better.