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目的 研究兔和大鼠静脉注射12 5I 激肽释放酶后的药代动力学。方法 12 5I标记结合分子排阻高效液相 (SHPLC)。结果 12 5I 激肽释放酶保持酶解生色底物S 2 2 6 6的生物活性 ,放化纯度 (95 2± 1 8) %。家兔静脉注射 5× 10 -3 、15× 10 -3 和 45× 10 -3 pNAU·kg-1剂量12 5I 激肽释放酶后与血浆蛋白质结合 ,t1/ 2α为 0 0 9～ 0 15h ,t1/ 2 β为 1 2 8～ 2 18h。曲线下面积与剂量成正比 ,而全身清除率相近。大鼠三氯醋酸 (TCA)可沉淀放射性 ,分布特点是 :泌尿排泄系统最高 ,血管丰富内脏组织较高 ,脑皮层最低。大鼠静脉注射12 5I 激肽释放酶后主要经尿排泄 ,少量经粪排泄 ;48h尿粪排出 (96 9±3 3) % ;12h胆汁排出 (7 9± 1 8) %。12 5I 激肽释放酶与兔血浆蛋白质结合的Bmax为 (94 3±0 77) % ,Kd 为 8 9× 10 -8mol·L-1。结论 家兔静脉注射12 5I 激肽释放酶后符合线性药代动力学 ,大鼠静脉注射12 5I 激肽释放酶后不能进入血脑屏障。
Objective To study the pharmacokinetics of 125I kallikrein in rabbits and rats. Method 12 5I labeling combined with molecular exclusion high performance liquid chromatography (SHPLC). Results 12 5I kallikrein maintained the biological activity of enzymatic chromogenic substrate S 2 2 6 6, and the radiochemical purity (95 2 ± 1 8)%. Rabbits were intravenously injected with 5 × 10 -3, 15 × 10 -3 and 45 × 10 -3 pNAU · kg -1 dose of 125I kallikrein and plasma protein binding, t1 / 2α was 0 0 9 ~ 0 15h, t1 / 2 β is 1 2 8 ~ 2 18h. The area under the curve is proportional to the dose, and the systemic clearance rate is similar. Rat TCA can precipitate radioactivity, the distribution is characterized by: the highest urinary excretion system, vascular rich visceral tissue, the lowest cortex. After intravenous injection of 125I kallikrein, rats were mainly excreted excreted by urine and excreted in a small amount by excrement. Urinary excretion was excreted in 48h (96 9 ± 3 3%) and excreted in 12h (7 9 ± 18%). The Bmax of 125I kallikrein bound to rabbit plasma protein was (94 3 ± 0 77)% and Kd was 8 9 × 10 -8 mol·L -1. Conclusion Rabbits intravenous injection of 125I kallikrein in line with the linear pharmacokinetics of rats after intravenous 125I kallikrein can not enter the blood-brain barrier.