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.

STUDY DESIGN AND 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.