1. The Pharmacokinetics and Pharmacodynamics of A Novel Recombinant Activated Human Factor VII, GEN-0828, in Hemophilia B Mice.
- Author
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Liu YL, Zhu XX, Niu LY, Gao Y, Gan H, Wu ZN, Li J, Feng SX, Dou GF, Gu RL, and Meng ZY
- Subjects
- Humans, Animals, Mice, Factor VII pharmacokinetics, Factor VII therapeutic use, Factor VIIa therapeutic use, Hemorrhage drug therapy, Recombinant Proteins, Hemophilia B drug therapy, Hemophilia A
- Abstract
GEN-0828, a proposed clinical candidate for hemophilia and trauma hemorrhage treatment, is a novel recombinant activated human factor VII (rFVIIa). The purpose of this paper is to compare the pharmacokinetics and pharmacodynamics of GEN-0828 in hemophilia B mice with those of NovoSeven®, the only marketed rFVIIa product worldwide., GEN-0828 and NovoSeven® showed similar affinity bioactivity to recombinant tissue factor (rTF) in vitro. Pharmacodynamics data indicated a generally similar hemostatic efficacy (ED
50 ) of GEN-0828 (10.91 KIU·kg-1 ) and NovoSeven® (18.91 KIU·kg-1 ) at the doses studied in hemophilia B mice, while GEN-0828 represented a lower initial effective dosage compared with that of NovoSeven® in terms of both blood loss and APTT. GEN-0828 exhibited linear pharmacokinetic profiles in hemophilia B mice at the 30-338 KIU·kg-1 dose range, the comparative pharmacokinetic study with NovoSeven® indicated better characteristics than NovoSeven® in terms of the appropriate higher maximal concentration (Cmax ) and area under the plasma concentration-time curve (AUClast ) and longer mean residence time (MRT). In conclusion, GEN-0828 was a promising new type of rFVIIa compound with favourable pharmacokinetic and pharmacodynamic profiles., Competing Interests: Declaration of Competing Interest No potential conflict of interest was reported by the authors., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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