兔股动脉血栓形成模型中国产重组葡激酶作用的实验研究  

An experimental study on pharmacokinetics of native r-SAK in a thrombosis model of the femoral artery in rabbits

作　　者：李春坚[1] 黄峻[1] 邵志高[2] 王蔚青[2] 杨国平[3] 黄蓬[3] 

机构地区：[1]南京医科大学第一附属医院心脏科,江苏省南京市210029 [2]南京医科大学第一附属医院药剂科,江苏省南京市210029 [3]南京医科大学第一附属医院动物实验室,江苏省南京市210029

出　　处：《中国临床康复》2004年第3期466-468,共3页Chinese Journal of Clinical Rehabilitation

摘　　要：目的:研究国产重组葡激酶(recombinantstaphylokinase,r-SAK)在兔股动脉球囊损伤后血栓形成模型中的药动学特征。方法:新西兰兔30只,采用随机抽签法分为6组,分别为对照组(生理盐水10mL,30min)、r-SAK小剂量组(r-SAK0.25mg/kg,30min)、r-SAK中剂量组(r-SAK0.5mg/kg,30min)、r-SAK大剂量组(r-SAK1.0mg/kg,30min)、r-SAK单次静脉推注组(r-SAK0.5mg/kg,2min)和联合肝素治疗组(先静脉推注肝素200U/kg,继之予r-SAK0.5mg/kg,30min,溶栓后予肝素50U/(kg·h)静滴至观察终点)。用球囊损伤法制作兔右股动脉血栓形成模型,模型形成后经耳缘静脉匀速输注治疗药物。溶栓前及溶栓后不同时间点取静脉血用“溶圈法”检测r-SAK血药浓度,用药代动力学计算程序拟合r-SAK药动学模型。结果:r-SAK血浆浓度在2.0×104～2.0×106U/L范围内与溶圈直径线性关系良好,平均回收率为(96.05±11.35)%,相对标准差(relativestandarddeviation,RSD)为±11.82%。各静脉输注组血药浓度峰值时间为30min,低、中、高3个剂量组峰值浓度与用药剂量呈正相关(r=0.99998,P<0.0001)。单次静脉推注组峰值浓度为(5.16±1.02)mg/L,显著高于等剂量30min输注组(P<0.01),其峰值时间为2min。联合肝素治疗组与等剂量r-SAK单独输注比较,峰值浓度差异无显著性意义(AIM:To study the pharmacokinetics of native recombinant staphylokinase(r- SA K) in a femoral artery balloon injury thrombosis model in rabbits. METHODS:Thirty New Zealand rabbits were randomly divided into six groups:cont rol group(saline 10 mL,30 min), r- SAK low dose group(0.25 mg/kg, 30 min), med ial dose group(0.5 mg/kg, 30min),high dose group(1.0 mg/kg, 30 min),single bolus group(0.5 mg/kg, 2 min) and conjunctive therapy group(initiated with heparin 20 0 U/kg,followed by infusion of r- SAK 0.5 mg/kg for 30 min,and subsequently inf used heparin 50 U/(kg· h) to endpoint).The thrombosis model of right femoral ar tery in rabbits was made by balloon injury,then the thrombolytic agents were inf used through parallel- ear vein and blood samples were collected pre- thrombol ysis and at different time post- thrombolysis to determine the plasma levels of r- SAK by lytic circle method, the plasma concentrations of r- SAK were proce ssed by pharmacokinetic computing procedure to fit the model. RESULTS:The plasma levels of r- SAK and the diameters of lytic circles showe d a pretty good linear correlation under the scope of 2.0× 104-2.0× 106 U/L, and the average recycle rate was (96.05± 11.35)% and relative standard devia tion(RSD) was± 11.82% .Peak concentration time in each infusion group was 30mi n,and the peak concentrations positively correlated with the doses administered in infusion groups(r=0.99998,P< 0.0001). In single bolus group,peak concentratio n time was 2 min, and the peak concentration reached(5.16± 1.02) mg/L,which was significant higher than that in same dose r- SAK infusion group(P< 0.01).In co njunctive therapy group,the peak concentration showed no significant difference from that in same dose r- SAK infusion group(P >0.05).The plasma concentration of r- SAK fit two- compartment model as processed by pharmacokinetic computing procedure. CONCLUSION:The lytic circle method is a simple,practical and reliable method to determine the plasma level of r- SAK,and the pharmacokinetics of native r- SAK in

关 键 词：兔 股动脉 血栓形成模型 中国 重组葡激酶 r-SAK 药动学 

分 类 号：R543[医药卫生—心血管疾病] R-332[医药卫生—内科学]