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• W1569674809 abstract "Summary 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 ½ ≈ 1·8 h. In contrast, PK profiles based on activity measurements were distinctly different. NN1731 induced a strong, short lasting ( t ½ ≈ 0·5 h) pro‐coagulant response, whereas rFVIIa induced a lower, longer lasting ( t ½ ≈ 1·1 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." @default.
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• W1569674809 date "2010-11-18" @default.
• W1569674809 modified "2023-10-18" @default.
• W1569674809 title "Intravascular inhibition of factor VIIa and the analogue NN1731 by antithrombin" @default.
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• W1569674809 doi "https://doi.org/10.1111/j.1365-2141.2010.08432.x" @default.
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