重组人粒细胞-巨噬细胞集落刺激因子和白细胞介素3融合蛋白在大鼠体内的药代动力学研究  

Pharmacokinetics of Recombinant GM-CSF/IL-3 Fusion Protein in Rats

作　　者：孙迎基[1] 吕厚峰[1] 廖建民[1] 张奉国[1] 刘煜[1] 沈子龙[1] 

机构地区：[1]中国药科大学生物技术中心,江苏南京210009

出　　处：《药物生物技术》2006年第5期355-359,共5页Pharmaceutical Biotechnology

摘　　要：研究重组人粒细胞-巨噬细胞集落刺激因子和白细胞介素3融合蛋白(GM-CSF/IL-3,MX)在大鼠体内的药代动力学。方法:实验采用同位素示踪技术结合HPLC分析,建立了MX在大鼠血浆中的测定方法,并测定了MX皮下注射3个剂量水平和静脉注射中剂量水平在大鼠体内的药动学参数。结果:高中低剂量T1/2分别为(1 5.4±2.0),(1 6.1±1.8)h,(1 3.2±2.2)h;AUC分别为(5 8 8±1 2 0),(2 8 6±4 7),(1 4 2±2 0)μg/(L.h),Cmax分别为(3 1.2±8.3),(1 4.8±1.2),(8.3±1.4)μg/L。结论:MX皮下注射给药后,Cmax和AUC与剂量成比例,MX在大鼠体内的代谢和消除是线性的。7 0μg/kg组生物利用度为3 5.6%。The pharmacokinetics of GM-CSF/IL-3 fusion protein was studied. An isotopic tracer method coupling with HPLC was established to determine the MX fusion protein in rat serum. Pharmacokinetics parameters of MX in rats were obtained at three-doses level by sc injection and one level by iv. The results showed that the biological half-life of MX at three-doses level by sc injection is （15.4±2.0）h, （16.1±1.8）, （13.2±2.2）h; The AUC is （588±120）, （286±47）, （142±20） g/（L·h） and the Cmax is （31.2±8. 3）, （14. 8±1. 2）, （8. 3±1. 4） μg/L. The Cmax and AUC of MX after sc injection were proportional to dose, which suggested that MX had the pharmacokinetics linearity over the dose range from 35μg/kg to 140μg/kg. The bioavailability of MX was approximately 35. 6% at the dose of 70μg/kg.

关 键 词：重组人粒细胞-巨噬细胞集落刺激因子和白细胞介素3融合蛋白 药代动力学 高效液相 

分 类 号：R969.1[医药卫生—药理学]