论文部分内容阅读
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 (P
OBJECTIVE: To study the pharmacokinetics of domestic recombinant staphylokinase (r SAK) in the thrombosis model of rabbit femoral artery after balloon injury, and to determine the level of r SAK in plasma by “lyse method”. Methods: Thirty New Zealand rabbits were randomly divided into control group (saline 10ml, 30min), r SAK low dose group (r SAK 0.25mg kg, 30min), r SAK medium dose group (r SAK 0.5mg kg, (R SAK 1.0 mg kg, 30 min), r SAK single intravenous injection (r SAK 0. 5 mg kg, 2 min), and heparin-treated group , Followed by r SAK 0 .5mg kg, 30min, heparin heparin after thrombolysis 50U (kg · h) intravenously to the end of observation). Rabbit right femoral artery thrombosis model was made by balloon injury method, then the infusion of thrombolytic drugs through the ear vein. Before and after thrombolysis, venous blood was taken at different time points to measure the plasma concentration of r-SAK by “lymphadenectomy” method. Pharmacokinetic calculation procedure was used to fit r-SAK pharmacokinetic model. Results: The plasma concentration of r-SAK had a good linear relationship with the diameter of the lysosome in the range of 2.0 × 10 4 ~ 2.0 × 10 6 UL, the average recovery was (96.0 ± 11.35)%, the relative standard deviation , RSD) was ± 11.82%. The peak time of plasma concentration in each intravenous infusion group was 30min. The peak concentration of low, middle and high dosage groups was positively correlated with the dosage (r = 0.99998, P <0.0001). The peak concentration of single intravenous bolus group was (5.16 ± 1.02) mg L, which was significantly higher than the 30min infusion group (P