title: A study of the pharmacokinetics and safety of recombinant activated factor VII in healthy Caucasian and Japanese subjects.
abstract: In this randomized, placebo-controlled, double-blind, single-centre, dose escalation study, we report the first evaluation of the pharmacokinetics and safety of recombinant activated factor VII (rFVIIa) in healthy Caucasian and Japanese subjects. Thirty-two healthy subjects were stratified according to sex and ethnic group to receive single bolus intravenous injections of three different doses of rFVIIa (40, 80, 160 microg/kg rFVIIa) or placebo, each separated by a 7-day wash-out period. Blood samples were taken up to 24 h after dosing. The factor VII clotting activity appeared to be dose dependent, but independent of sex and ethnic group. Statistical analyses demonstrated no significant effect of dose, sex or ethnicity on the dose-normalized mean area under the plasma concentration-time curve AUC0-t, indicating dose proportionality. No serious adverse events or thromboembolic events were reported. Analyses of coagulation parameters did not suggest induction of systemic coagulation when dosing rFVIIa up to 160 microg/kg. In conclusion, the pharmacokinetics of rFVIIa in Caucasian and Japanese subjects are similar, and no safety issues were identified.
authors.affiliation: Novo Nordisk A/S, Krogshoejvej 55, DK-2880 Bagsvaerd, Denmark. eer@novonordisk.com
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Fridberg
authors.forename: Ulla
authors.initials: U
authors.lastname: Hedner
authors.forename: Harold R
authors.initials: HR
authors.lastname: Roberts
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Erhardtsen
mesh_terms: D000328:Adult; D019540:Area Under Curve; D044466:Asian People; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005167:Factor VII / Q000009:adverse effects / Q000493:pharmacokinetics*; D015942:Factor VIIa; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010599:Pharmacokinetics; D011994:Recombinant Proteins / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D044465:White People
chemical_list: D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa