聚乙二醇化重组人白细胞介素-6经不同途径给药的药代动力学比较研究

Comparison of Pharmacokinetics PEG-rhIL-6 at Different Methods of Administration in Rat

目的研究聚乙二醇化重组人白细胞介素-6不同给药途径的药代动力学。方法将大鼠分为皮下给药组、静脉给药组,每组各设3个剂量组。分别按40μg/kg、20μg/kg、3μg/kg给药。同位素示踪法用碘标记PEG-rhIL-6,采用TCA沉淀法检测放射性浓度,3P87软件判断房室模型并计算各种参数,并检测125I-PEG-rhIL-6皮下注射大鼠后不同时间的血药浓度。结果①静脉给药大鼠体内的血药浓度-时间曲线符合二房室模型,而皮下给药大鼠体内的血药浓度-时间曲线符合一房室模型;②皮下给药的达峰时间比静脉给药慢,但其有效血药浓度维持时间较静脉给药长;③皮下给药较静脉给药各时点血药浓度低。结论皮下给药毒性低,是一种安全可靠的给药方法;同时有效血药浓度维持时间较长,有利于治疗血小板减少症。

Objective To study the different pharmaeokinetics of PEG-rhlL-6 at different methods of administration in rat. Methods Rats were divided into two groups： one group administration of PEG-rhlL-6 via subcutaneous and the other via vein. Three different doses （40 μg/kg, 20μg/kg, 3 μg/kg） were given to different groups. Pharmacokinetics and distribution of PEG-rhIL-6 in rats were studied by 125I isotope tracing method. Pharmacokinetic analysis was performed using 3P97 computer software. Results Upon administration, PEG-rhIL-6 fitted to two-compartment model after administration via vein, while PEG-rhIL-6 fitted to one-compartment model after administration via subcutaneous. The Tmax of PEG-rhIL-6 after administration via vein was faster than via subcutaneous, but the concentration of PEG-rhIL-6 in blood were always relativity low at various time points and sustained a long time after administration via subcutaneous. Conclusion The method of administration via subcutaneous was better than via vein in this study.