【摘要】 目的研究重组水蛭素-2(rHV2)喷雾剂鼻腔给药后在大鼠体内的药代动力学过程及其抗凝血作用。方法采用呈色肽法测定大鼠鼻腔给予rHV2喷雾剂后血浆中rHV2的浓度,并计算其药代动力学参数;考察rHV2鼻腔喷雾剂对正常大鼠和弥散性血管内凝血模型(D IC)家兔凝血时间的影响。结果rHV2喷雾剂鼻腔给药后,rHV2的体内过程符合一室模型,其相对生物利用度为28.53%;rHV2鼻腔喷雾剂可使正常大鼠活化的部分凝血活酶时间(APTT)和凝血酶时间(TT)明显延长,使D IC模型家兔的APTT凝血时间明显缩短,接近正常值。结论药代动力学和药效学结果证明,rHV2鼻腔喷雾剂有望成为rHV2鼻腔给药的有效制剂。更多还原

【Abstract】 Aim To investigate the pharmacokinetics and the anticoagulation action of recombinant hirudin-2(rHV2) nasal spray after administration of the preparation.Methods rHV2 concentration in plasma was determined by chromogenic substrate method and the relative bioavailability was calculated.The anticoagulation action of rHV2 spray after intranasal administration in normal rats and DIC model rabbits after intranasal administration of rHV2 spary were studied.Results The in vivo course of rHV2 in rats fitted to the one-compartment model after intranasal administration of rHV2 spray and the relative bioavailability was 28.53%.Coagulating times of APTT and TT were significantly prolonged in normal rats,and APTT in DIC model rabbits was significantly shortened and was close to the normal values after administration of rHV2 nasal spray.Conclusion rHV2 spray could be an effective nasal preparation of rHV2.更多还原