Overview of the human pharmacokinetics of recombinant activated factor VII.
OBJECTIVE
To review the pharmacokinetics of rFVIIa in various patient populations, and to discuss the differences observed between groups.


METHODS
Based on a registry of Novo Nordisk studies, 14 studies evaluating rFVIIa pharmacokinetics following single and multiple bolus administration in healthy volunteers, adult and paediatric patients with congenital haemophilia and inhibitors, patients undergoing liver surgery and in patients with cirrhosis, inherited FVII deficiency, upper gastrointestinal bleeding or severe trauma were identified. Data on rFVIIa PK, analyzed with noncompartmental and population pharmacokinetic methods, were extracted.


RESULTS
Plasma clearance was a more robust parameter than half-life for comparing rFVIIa pharmacokinetics between groups. In healthy volunteers and patients with no or low-level bleeding (e.g. adults with haemophilia, nonbleeding patients with cirrhosis), plasma clearance was relatively low (30-40 ml kg(-1) h(-1)). In children with haemophilia and adults with high-level bleeding (e.g. cirrhotic patients undergoing orthotopic liver transplantation or resection) and patients with congenital FVII deficiency, plasma clearance was relatively higher (60-90 ml kg(-1) h(-1)).


CONCLUSIONS
Comparison of plasma clearance rates in different patient populations suggested that subjects fall into two distinct groups. These differences may have clinical implications in terms of how to adapt the rFVIIa dosing regimen, depending on the expected bleeding rate/blood loss and underlying disease.
Klitgaard
Thomas
T
Department of Biomodelling, Novo Nordisk A/S, Bagsvaerd, Denmark. tkt@novonordisk.com
Nielsen
Tina G
TG
D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001760:Bleeding Time; D002648:Child; D002675:Child, Preschool; D015942:Factor VIIa / Q000493:pharmacokinetics*; D006467:Hemophilia A / Q000188:drug therapy*; D002836:Hemophilia B / Q000188:drug therapy*; D006470:Hemorrhage / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D011994:Recombinant Proteins / Q000493:pharmacokinetics
D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa