title: Pharmacokinetic properties of two different recombinant activated factor VII formulations.
abstract: Recombinant factor VIIa is indicated for treatment of bleeding episodes in patients with haemophilia A or B with inhibitors; in FVII deficiency and in Glanzmann's thrombasthenia. The aim of the study reported here was to compare the pharmacokinetic profiles between two formulations of rFVIIa that are produced in two different cell lines and media: Chinese hamster ovary cells cultured in a serum-free medium (CHO-rFVIIa) and baby hamster kidney cells cultured in a non-human serum-based medium (BHK-rFVIIa). Two clinical trials were performed; one in healthy subjects and the other in patients with congenital haemophilia A or B, with or without inhibitors. Subjects were recruited into a two-way crossover trial and were randomized to receive a dose of CHO-rFVIIa and BHK-rFVIIa. Healthy subjects received one dose of 90 μg CHO-rFVIIa kg(-1) bodyweight (bw) in the newly developed room-temperature stable rFVIIa formulation and one dose of 90 μg BHK-rFVIIa kg(-1) bw, in the original rFVIIa formulation. Patients with haemophilia received one dose of 270 μg CHO-rFVIIa kg(-1) and one dose of 270 μg BHK-rFVIIa kg(-1), both in the room-temperature stable formulation. The trials showed higher FVII activity levels [higher area under the plasma concentration-time curve (AUC)] following administration of CHO-rFVIIa than after BHK-rFVIIa. Therefore, bioequivalence could not be established. The difference in FVII activity levels is believed to be a result of different glycosylation patterns between the two products. Neither the use of CHO-rFVIIa nor the use of one single dose of 270 μg kg(-1) of the newly developed room-temperature stable rFVIIa raised any safety concerns.
authors: Agency for Haemophilia, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy. massimo.morfini@unifi.it
authors: M
authors: M
authors: Morfini
authors: V
authors: V
authors: Jiménez-Yuste
authors: H
authors: H
authors: Eichler
authors: R
authors: R
authors: Fischer
authors: C M
authors: CM
authors: Kirchmaier
authors: B
authors: B
authors: Scharling
authors: J
authors: J
authors: Bjerre
mesh_terms: D000328:Adult; D019540:Area Under Curve; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D003029:Coagulants / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D015942:Factor VIIa / Q000493:pharmacokinetics*; D006467:Hemophilia A / Q000188:drug therapy / Q000378:metabolism*; D002836:Hemophilia B / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D003029:Coagulants; D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa