Pharmacokinetic analysis of plasma-derived and recombinant F IX concentrates in previously treated patients with moderate or severe hemophilia B.
BACKGROUND
Hemophilia B is an X-linked bleeding disorder that affects approximately 1 in 25,000 males. Therapy for acute bleeding episodes consists of transfusions of plasma-derived (pd-F IX) or recombinant (r-F IX) concentrates.


METHODS
A double-blind, two-period crossover study was initiated to assess the pharmacokinetics of pd-F IX and r-F IX and to address patient-specific variables that might influence in vivo recovery. Study product was administered by a single bolus infusion (50 IU/kg) to 43 previously treated patients in the nonbleeding state, and F IX:C levels were measured over a period of 48 hours after infusion.


RESULTS
The mean in vivo recovery in the pd-F IX group was 1.71 +/- 0.73 IU per dL per IU per kg compared with 0.86 +/- 0.31 IU per dL per IU per kg with r-F IX (p <or= 0.0001). There was a significant positive correlation (Pearsons r = 0.62, p <or= 0.0001, 95% CI, 0.37-0.78) between the recoveries of the two products and a weak correlation between the recovery of pd-F IX and baseline F IX:Ag levels. There was no significant difference in the terminal half-lives of the two products.


CONCLUSIONS
The study found wide product- and patient-related variability in recovery. Inherent differences among patients, including baseline F IX, may account for some of the interpatient variability. These differences should be taken into account in optimizing treatment regimens for individual patients with hemophilia B.
Ewenstein
Bruce M
BM
Hematology Division, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. bewenstein@partners.org
Joist
J Heinrich
JH
Shapiro
Amy D
AD
Hofstra
Thomas C
TC
Leissinger
Cindy A
CA
Seremetis
Stephanie V
SV
Broder
Martin
M
Mueller-Velten
Guenther
G
Schwartz
Bruce A
BA
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005164:Factor IX / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D002836:Hemophilia B / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics
D011994:Recombinant Proteins; D005164:Factor IX