重组水蛭素在家兔体内生物半衰期的测定

Determination of the biological half-life of recombinant hirudin in rabbits

目的通过对重组水蛭素(rH)在家兔体内的抗凝活性生物半衰期的测定,为rH的临床应用和治疗药物监测提供实验资料。方法家兔i.v.rH前及后采血,用血凝仪测定活化的部分凝血活酶时间(APTT),基于其量效关系和时效关系,确定rH抗凝活性消除动力学类型,并计算抗凝活性生物半衰期(t1/2(E))。结果rH对APTT呈剂量依赖性延长,在rH 12.5-100.0μg/kg的剂量范围内呈良好线性(r=0.9612)。APTT延长%经对数转换与i.v.50.0μg/kgrH药后时间呈线性相关(r=0.9901),其抗凝活性消除动力学属于一级动力学,求得其t1/2(E)为26.64 min。结论rH抗凝活性在体内衰减快速,进一步支持临床采用静脉滴注给药,以及在治疗药物监测时首选APTT为指标。

Objective To determine the biological half-life （t1/2（E）） of recombinant hirudin （rH） anticoagulant activity and provide experimental data for the clinical application and therapeutic drug monitoring of rH.Methods Activated partial thromhoplastin time （APTT） were determined by coagulometer for rabbit blood samples collected before and after i.v.rH.Based on the dose- and time-effect relationship of rH, the elimination kinetic model of rH anticoagulant activity was ascertained. And t1/2（E）was calculated. Results rH prolonged APTT dose- and time-dependently in the range of 12.5 - 100.0μg/kg（ r = 0.9612）. The plot of APTT prolongation percent against postdcse time at i.v.50.0 μg/kg rH showed good linearity （ r = 0.9901） .The rH anticoagulant activity decay could be described best by the first-order kinetics,with t1/2（E）being 26.64 rain. Conclusion rH anticoagulant activity decreases rapidly in body, which suggests that rH should be administrated by i. v. gtt in clinic, and APTT be selected as therapeutic drug monitoring index firstly.