重组葡激酶在大鼠静脉注射给药后的药代动力学

Pharmacokinetics of Recombinant Staphylokinase in Rats after Bolus Injection

目的 研究重组葡激酶 (r Sak)在大鼠静脉注射后的药代动力学。方法 大鼠静注r Sak 10 0、30 0与90 0 μg·kg-1,采用生物免疫发色底物法和牛奶板溶圈法测定活性 ,以单抗测定含量。结果 r Sak静注后 ,在大鼠体内过程符合二室模型。测定活性表明 ,3种剂量r Sak的T1/2α分别为 (1.79± 0 .76 )、(1.99± 0 .6 0 )及(2 .2 2± 1.0 1)min ;T1/2 β分别为 (2 0 .2 4± 11.15 )、(2 5 .32± 9.2 6 )及 (2 6 .45± 11.6 4)min ;AUC0 T 分别为(182 .88± 6 4.0 7)、(376 .2 6± 71.14)及 (1311.4± 36 9.4)HI·min·mL-1;测定含量表明 ,3种剂量r Sak的T1/2α分别为 (1.5 8± 0 .86 )、(1.2 2± 0 .5 7)及 (1.49± 0 .47)min ;T1/2 β分别为 (16 .5 8± 6 .75 )、(12 .94± 3.13)及 (15 .5 4± 3.88)min ;AUC0 T分别为 (2 .0 5± 0 .75 )、(5 .6 5± 2 .5 3)及 (13.18± 5 .43) μg·min·mL-1。结论 r Sak在大鼠体内过程符合二室模型 ,经方差检验 ,各剂量间药代动力学参数均无显著性差异 (P >0 .0 5 )。

Purpose: To study the pharmacokinetics of recombinant staphylokinase (r-Sak) in rats after bolus injection via caudal vein. Methods: Rats were injected r-Sak 100 300 and 900 μg&middotkg-1 iv via caudal vein. The activities of r-Sak were determined by choromogenic substrate and milk-agrose plate assay, and the contents of r-Sak were determined using monoclonal antibody. Results: r-Sak after iv in rats was fitted with 2-compartment model. The pharmacokinetic parameters of r-Sak activities at 3 doses were as follows: T1/2α: (1.79 ± 0.76) (1.99 ± 0.60) and (2.22 ± 1.01) min; T1/2β: (20.24 ± 11.15), (25.32 ± 9.26) and (26.45 ± 11.64) min; AUC 0-T: (182.88 ± 64.07), (376.26 ± 71.14) and (1 311.4 ± 369.4) HI&middotmin&middotmL-1; The pharmacokinetic parameters of r-Sak contents at 3 doses were as follows: T1/2α : (1.58 ± 0.86), (1.22 ± 0.57) and (1.49 ± 0.47) min; T1/2β: (16.58 ± 6.75), (12.94 ± 3.13) and (15.54 ± 3.88) min; AUC0-T: (2.05 ± 0.75), (5.65 ± 2.53) and (13.18 ± 5.43) μg&middotmin&middotmL -1. Conclusions: r-Sak after iv in rats was fitted with 2-compartment model, and there were no significant differences among the pharmacokinetic parameters at 3 doses (P>0.05).