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Pharmacokinetic and pharmacodynamic properties of plasma‐derived vs. recombinant factor IX in patients with hemophilia B: a prospective crossover study
Author(s) -
Alamelu J.,
Bevan D.,
Sorensen B.,
Rangarajan S.
Publication year - 2014
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12756
Subject(s) - crossover study , pharmacokinetics , factor ix , pharmacodynamics , medicine , washout , regimen , prospective cohort study , bioequivalence , pharmacology , alternative medicine , pathology , placebo
Summary Background Effective treatment of acute bleeding episodes in patients with hemophilia B relies on factor IX recovery, with higher levels being more desirable, whereas prevention of bleeds with a prophylactic regimen depends on the half‐life of the product. Lower recovery values have been reported following administration of recombinant FIX ( rFIX ) than following administration of plasma‐derived FIX (pdFIX). Objectives To compare the pharmacokinetic and pharmacodynamic properties of rFIX and pdFIX in patients with hemophilia B. Methods A prospective crossover study of nine patients with moderate to severe hemophilia B was performed. Following a washout period, 50 U kg −1 FIX was administered, and blood samples were taken as per protocol up to 48 h postinfusion. Paired data were analyzed with the Wilcoxon signed rank test. Results Mean peak recovery at 10 min postinfusion was 62.14 IU dL −1 with pdFIX and 52.7 IU dL −1 with rFIX ( P = 0.08). Mean half‐life was 16.6 h with pdFIX and 17.5 h with rFIX ( P = 0.55). Maximum peak thrombin generation (PTG) was 35.9 n m with pdFIX and 28.9 n m with rFIX ( P = 0.21). Administration of rFIX resulted in early PTG, whereas administration of pdFIX resulted in slightly later and sustained PTG. At 48 h, PTG was similar with pdFIX (19.0 n m ) and rFIX (19.4 n m ) ( P = 0.91). Conclusions Patients experienced better recovery with pdFIX than with rFIX . pdFIX and rFIX had similar half‐lives. Maximum PTG was higher for pdFIX; however, this difference did not reach statistical significance. The clinical impact of the slightly increased, delayed and sustained PTG with pdFIX requires further investigation.