摘要
Objective: To study the pharmacokinetics of native r SAK in rabbit's femoral artery thrombosis model, the “lytic circle' method was used to determine plasma levels of r SAK. Methods: Thirty New Zealand rabbits were randomly assigned to the control (saline 10 ml, 30 min), r SAK low dose (0.25 mg/kg, 30 min), medial dose (0.50 mg/kg, 30 min), high dose (1.00 mg/kg, 30 min), single bolus (0.50 mg/kg, 2 min) and conjunctive therapy (initiated with heparin 200 U/kg, followed by infusion of r SAK 0.50 mg/kg for 30 min, and subsequently infused heparin 50 U/(kg·h) to endpoint) groups. The right femoral artery thrombosis model in rabbit was made by balloon injury, then the thrombolytic agents were infused through parallel ear vein and the blood samples were collected pre thrombolysis and at different time post thrombolysis to determine the plasma levels of r SAK by “lytic circle' method, the plasma levels of r SAK were processed by pharmacokinetic computing procedure to fit the model. Results: The plasma levels of r SAK and the diameters of lytic circles showed a pretty good linear correlation under the scope of 2.0×10 4 2.0×10 6 U/L, and the averaged recycle rate was (96.05±11.35)%(RSD =±11.82%).All peak concentration time in each infusion group was 30 min, and the peak concentrations positively correlated with the doses administrated in infusion groups(r=0.999 98, P <0.000 1). In single bolus group, Peak concentration time was 2 min, and the peak concentration reached (5.16±1.02) mg/L, which was significant higher than that in the same dose r SAK infusion group ( P <0.01). In conjunctive therapy group, the peak concentration showed no significant difference from that in the same dose r SAK infusion group ( P >0.05). The plasma levels of r SAK fit in two compartment model as processed by pharmacokinetic computing procedure in each group. 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 infusion fits in two compartment model in rabbit's femoral artery thrombosis model.
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代动力学特征 ,采用“溶圈法”测定血浆r SAK水平。方法 :新西兰兔 30只 ,随机分为对照组 (生理盐水 10ml,30min)、r SAK小剂量组 (r SAK 0 .2 5mg kg ,30min)、r SAK中剂量组 (r SAK 0 .5mg kg ,30min)、r SAK大剂量组(r SAK 1.0mg 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 2 0 0U kg ,继之予r SAK 0 .5mg kg ,30min ,溶栓后予肝素5 0U (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 ,然后经耳缘静脉匀速输注溶栓药物。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药代动力学模型。结果 :r SAK血浆浓度在 2 .0× 10 4 ～ 2 .0× 10 6 U L范围内与溶圈直径线性关系良好 ,平均回收率为 (96 .0 5±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 .0 0 0 1)。单次静脉推注组峰值浓度为 (5 .16± 1.0 2 )mg L ,显著高于等剂量 30min输注组
