The features of clearance in recombinant factor IX (BeneFIX(®) )

Introduction: Dosage adjustment is very important to perform continuous infusion (CI) of recombinant factor IX (rFIX) concentrates more effectively and economically, and clearance (CL) is strongly related to the infusion rate. However, previous reports have shown that the CL of rFIX concentrates varies widely (4.2-11.4 mL kg(-1) h(-1) ).

Aim: The goal of this study was to gain a better understanding of the CL of the rFIX concentrate (BeneFIX(®) ) to precisely set the infusion rate of rFIX concentrates.

Methods: We estimated CLs by five different calculation approaches: from area under the blood concentration-time curve (AUC), from in vivo recovery (IVR) and half-life, from actual FIX activity value during CI, and from the simulation by one-compartment model in seven patients with haemophilia B.

Results: The mean CL calculated from AUC was 3.8 ± 0.4 mL kg(-1) h(-1) (range = 3.3-4.3 mL kg(-1) h(-1) ).

Conclusion: The mean CL calculated from IVR and distribution half-life was 4.4 ± 0.4 mL kg(-1) h(-1) (range = 4.0-5.1 mL kg(-1) h(-1) ). The mean CL calculated from IVR and terminal half-life was 2.1 ± 0.5 mL kg(-1) h(-1) (range = 1.7-2.8 mL kg(-1) h(-1) ). The mean CL during CI was 4.9 ± 0.6 mL kg(-1) h(-1) (range = 4.2-5.6 mL kg(-1) h(-1) ). In addition, when we simulated the theoretical CL using a one-compartment model, the adjusted mean CL during CI was 4.8 ± 0.5 mL kg(-1) h(-1) (range = 4.0-5.4 mL kg(-1) h(-1) ). The CL obtained from distribution half-life was comparable to the CL during CI, while the CL calculated from terminal half-life did not reflect actual CL. Further, the rFIX concentrate was characterized by a one-compartment model under certain conditions.