title: Pharmacokinetic and pharmacodynamic properties of plasma-derived vs. recombinant factor IX in patients with hemophilia B: a prospective crossover study.
abstract: 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).
  
  
  OBJECTIVE
  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 nm with pdFIX and 28.9 nm 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 nm) and rFIX (19.4 nm) (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.
authors.affiliation: Centre for Haemostasis and Thrombosis, Guy's and St Thomas' NHS Foundation Trust, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Alamelu
authors.forename: D
authors.initials: D
authors.lastname: Bevan
authors.forename: B
authors.initials: B
authors.lastname: Sorensen
authors.forename: S
authors.initials: S
authors.lastname: Rangarajan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018592:Cross-Over Studies; D005164:Factor IX / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002836:Hemophilia B / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D015203:Reproducibility of Results; D013917:Thrombin / Q000737:chemistry; D013997:Time Factors; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D005164:Factor IX; D013917:Thrombin
keywords: factor IX; half-life; hemophilia B; pharmacodynamics; pharmacokinetics