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The features of clearance in recombinant factor IX (BeneFIX ® )
Author(s) -
Suzuki N.,
Takedani H.,
Hirakawa A.,
Ushijima Y.,
Matsushita T.
Publication year - 2015
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/hae.12672
Subject(s) - factor ix , haemophilia , medicine , half life , distribution (mathematics) , plasma clearance , pharmacokinetics , nuclear medicine , surgery , mathematics , mathematical analysis
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 CL s 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.