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目的 研究重组人粒 /巨噬细胞集落刺激因子 白细胞介素 3融合蛋白 (PIXY32 1)在猕猴中的药动学。方法 12 5I 标记结合反相高效液相和酸沉淀法。结果 12 5I PIXY32 1纯度为 94 5 % ,标记前后PIXY32 1对TF 1细胞增殖的ED50 分别为 0 12 5和 0 119μg·L-1。12 5I PIXY32 1在体内迅速降解。iv和sc后末端T1/ 2 相近 ,为 6 6～ 8 2h。AUC随sc剂量增大 ,全身清除率ClS 相近 ,sc生物利用度6 3 %± 2 1%。泌尿系统浓度最高 ,胆汁其次 ,骨髓和脾脏高于其它组织略低于血清 ,脑内最低。主要经尿排泄 ,少部分在尿中以原型排出。结论 猕猴sc12 5I PIXY32 12 0～ 80 μg·kg-1后为线性药代动力学。肾脏在12 5I PIXY32 1的降解中起一定作用
Objective To study the pharmacokinetics of recombinant human granulocyte / macrophage colony stimulating factor interleukin-3 fusion protein (PIXY32 1) in rhesus monkeys. Method 12 5I labeling combined with RP HPLC and acid precipitation. Results The purity of 12 5I PIXY32 1 was 94.5%. The ED50 of PIXY32 1 on the proliferation of TF 1 cells before and after labeling were 0 12 5 and 0 119 μg · L-1.12 5I PIXY32 1, respectively. iv and sc after the terminal T1 / 2 similar to 6 6 ~ 8 2h. AUC increased with sc dose, systemic clearance rate ClS similar, sc bioavailability 6 3% ± 21%. Urinary system highest concentration, followed by bile, bone marrow and spleen higher than other tissues slightly lower than the serum, the lowest brain. The main excretion of urine, a small part of the urine in the prototype discharge. Conclusions Rhesus monkey sc12 5I PIXY32 linear pharmacokinetics after 12 0 ~ 80 μg · kg-1. The kidneys play a role in the degradation of 12 5I PIXY32 1