The pharmacokinetics and pharmacodynamics of single-dose and multiple-dose recombinant activated factor VII in patients with haemophilia A or B.

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To compare the pharmacokinetics (PK) of rFVIIa after 3×90μgkg-1 doses vs a single dose (270μgkg-1 ) in haemophilia patients and to evaluate TEG/TGA results postdosing to determine how these assays relate to PK findings. Patients in this open-label, single-centre, randomized, crossover trial received one injection of 270μgkg-1 rFVIIa crossed over with three injections of 90μgkg-1 rFVIIa in a non-bleeding state. For TEG, kaolin and tissue factor were used as activators; TGA was performed on frozen platelet-rich and platelet-poor plasma, with and without corn trypsin inhibitor. FVIIa activity was evaluated using in vivo samples. TGA showed a dose-dependent effect of rFVIIa on thrombin generation; TEG revealed lower dose-dependent effects. Both showed some differences between single-/multiple-dose rFVIIa; both supported the PK findings. While TEG and TGA are not yet clinically predictive, both supported the PK results. Data suggest that, while a single dose of 270μgkg-1 rFVIIa provides slightly higher haemostatic potential than the multiple-dose regimen of 3×90μgkg-1 , the latter results in prolonged activity levels compared with a higher single dose.