枯草芽孢杆菌纤溶酶的生物分析方法及其在猕猴体内的药动学研究

目的：研究猕猴单次静脉滴注注射用枯草芽孢杆菌纤溶酶（BSFE）的药动学。方法：6只猕猴静脉滴注BSFE2.5mg/kg,采用ELISA法测定动物的血药浓度,实验数据用DAS2.0药动程序拟合并计算药动参数。结果：6只猕猴静脉滴注2.5mg/kg的BSFE,浓度-时间数据经药代动力学参数计算,表明药物消除符合二房室模型。6只猕猴的达峰时间（tmax）均为0.5h,峰浓度（Cmax）均值为（592.3±150.9）μg/L;平均消除t1/2β为（5.78±1.19）h;平均清除率（CL）为（4.42±1.19）L.h^-1.kg^-1;药时AUC0-24.5h均值为（557.1±211.1）μg.L^-1.h。结论：本试验所建立的双抗体夹心ELISA法,灵敏度高、特异性强、操作简便,适于BFSE的药代动力学研究。

Bioanalytical method and pharmacokinetics of Bacillus subtilis fibrinolytic enzyme in rhesus monkeys

AIM:To characterize the pharmacokinetic properties of a Bacillus subtilis fibrinolytie enzyme(BSFE)following intravenous infusion in rhesus monkeys.METHODS:Six monkeys received single intravenous infusion doses of BSFE at 2.5 mg/kg.Serum concentration of BSFE was measured at various time-points after dosing by ELISA.Pharmacokinetic parameters were calculated with DAS 2.0 software.RESULTS:The concentration0time profile of BSFE in monkeys was described by a two-compartment model.The mean time to reach peak concentration(t_(max))was 0.5 h.The mean peak concentration(C_(max))was(592.3±150.9)μg/L.The mean elimination half-life(t_(1/2β))was(5.78±1.19)h.The mean drug clearance from the serum(CL)was(4.42±1.19)L·h~(-1)·kg~(-1).The mean area under the serum concentration-time curve (AUC_(0-24.5 h))was(557.1±211.1)μg·L~(-1)·h.CONCLUSION:A sandwich ELISA method is sensitive,high specificity and convenient,suitable for the determination of BSFE in serum and its pharmacokinetics studies.