Pharmacokinetics of Native r-SAK in Rabbit's Femoral Artery Thrombosis Model

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-SAK0.50 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 x10~4-2.0x 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. Con-clusion: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.