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首页> 外文期刊>British Journal of Haematology >Intravascular inhibition of factor VIIa and the analogue NN1731 by antithrombin.
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Intravascular inhibition of factor VIIa and the analogue NN1731 by antithrombin.

机译：抗凝血酶对因子VIIa和类似物NN1731的血管内抑制。

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摘要

NN1731 is a recombinant activated factor VII (rFVIIa) analogue with increased intrinsic activity. This also applies to its reactivity towards antithrombin (AT), the role of which was investigated in a pharmacokinetic (PK) study. NN1731 or rFVIIa was administered to normal and haemophilia A dogs and elimination was measured by FVIIa clot activity, FVIIa- and FVIIa-AT antigen. In vitro AT complex formation was studied in canine plasma spiked with NN1731 or rFVIIa. Based on FVIIa antigen concentrations, PK profiles in normal and haemophilia A dogs were similar for NN1731 and rFVIIa with antigen half lives, t(? H1? h. In contrast, PK profiles based on activity measurements were distinctly different. NN1731 induced a strong, short lasting (t(? H0? h) pro-coagulant response, whereas rFVIIa induced a lower, longer lasting (t(? H1? h) response. Western Blot and FVIIa-AT antigen analysis demonstrated in vivo AT complex formation that accounted for these divergences. AT complex formation with FVIIa or NN1731 in vitro in canine plasma was considerably slower than the in vivo reaction. The results suggest that in vivo inhibition by AT contributes significantly to define drug duration in haemophilia treatment with rFVIIa and in particular with the NN1731 analogue.
机译：NN1731是一种重组活化因子VII（RFVIIA）类似物，其内在活性增加。这也适用于对抗凝血酶（AT）的反应性，其作用在药代动力学（PK）研究中研究。施用NN1731或RFVIIa以正常和血毛利毒性，通过FVIIA凝块活性，FVIIA和FVIIA - 在抗原测量狗和消除。在甘氨酸血浆中研究了复杂形成的体外，掺入NN1731或RFVIIa。基于FVIIA抗原浓度，正常和血友病犬的PK型材类似于NN1731和RFVIIA，抗原半衰期，T（αH1〜H.相反，基于活性测量的PK简谱明显不同。NN1731诱导强烈，持续的（t（？H0？H）促凝血反应，而RFVIIa诱导较低，更长的持久性（T（αH1≤H）反应。Western印迹和FVIIA-in抗原分析，在占核对的复杂形成中的体内展示这些分歧。在犬素体外的FVIIA或NN1731的复杂形成比体内反应相当慢。结果表明，在体内抑制通过显着的抑制，以定义血友病治疗中的药物持续时间与RFVIIA，特别是NN1731类似物。

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