title: The features of clearance in recombinant factor IX (BeneFIX(®) ).
abstract: BACKGROUND
  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) ).
  
  
  OBJECTIVE
  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) ).
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
authors: N
authors: N
authors: Suzuki
authors: Department of Joint Surgery, Institute of Medical Science, University of Tokyo Research Hospital, Tokyo, Japan.
authors: H
authors: H
authors: Takedani
authors: Biostatistics Section, Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
authors: A
authors: A
authors: Hirakawa
authors: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Y
authors: Y
authors: Ushijima
authors: Department of Transfusion Medicine, Nagoya University Hospital, Nagoya, Japan.
authors: T
authors: T
authors: Matsushita
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D005164:Factor IX / Q000493:pharmacokinetics*; D006801:Humans; D008875:Middle Aged; D011994:Recombinant Proteins / Q000493:pharmacokinetics*
chemical_list: D011994:Recombinant Proteins; D005164:Factor IX
keywords: clearance; continuous infusion; haemophilia B; pharmacokinetics; recombinant factor IX