title: Pharmacokinetics of a high-purity plasma-derived factor X concentrate in subjects with moderate or severe hereditary factor X deficiency.
abstract: BACKGROUND
  Hereditary factor X (FX) deficiency affects 1:500 000 to 1:1 000 000 of individuals. There are few published data on the pharmacokinetics (PK) of FX for existing treatments for FX deficiency, and no specific replacement factor concentrate exists. A high-purity plasma-derived FX concentrate (pdFX) has been developed for use as replacement therapy in subjects with hereditary FX deficiency.
  
  
  OBJECTIVE
  This analysis assessed pdFX PK after a single 25 IU kg(-1) bolus dose in subjects with hereditary moderate or severe FX deficiency (plasma FX activity [FX:C] <5 IU dL(-1) ).
  
  
  METHODS
  For a baseline PK assessment, blood samples were taken predose and at intervals up to 144 h (7 days) post dose. After ≥6 months of on-demand pdFX treatment and treatment of ≥1 bleed with pdFX, subjects underwent repeat PK assessment. Samples were assayed for plasma FX:C (measured using the clotting and chromogenic assays) and FX antigen.
  
  
  RESULTS
  FX:C peaked at 0.4-0.5 h and subsequently declined over the course of 144 h with a biphasic decay curve. PK parameters observed at the baseline (n = 16) and repeat (n = 15) assessments were equivalent, therefore summary PK values were obtained by combining data from both visits (n = 31). The mean terminal half-life and incremental recovery of pdFX was 29.4 h and 2.00 IU dL(-1) per IU kg(-1) respectively.
  
  
  CONCLUSIONS
  This is the most comprehensive PK study to date in subjects with hereditary FX deficiency. These results are consistent with the observed haemostatic efficacy of pdFX and provide the PK data required for the treatment of hereditary FX deficiency using pdFX replacement therapy.
authors.affiliation: St. George's Haemophilia Centre, St. George's Hospital University NHS Foundation Trust, London, UK.
authors.forename: S K
authors.initials: SK
authors.lastname: Austin
authors.affiliation: KinetAssist Ltd, Quothquan, UK.
authors.forename: C
authors.initials: C
authors.lastname: Brindley
authors.affiliation: Faculty of Medicine, Children's Hospital, Ege University, Izmir, Turkey.
authors.forename: K
authors.initials: K
authors.lastname: Kavakli
authors.affiliation: Bio Products Laboratory Ltd., Elstree, UK.
authors.forename: M
authors.initials: M
authors.lastname: Norton
authors.affiliation: Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Shapiro
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001780:Blood Coagulation Tests; D002648:Child; D003029:Coagulants / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005170:Factor X / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005171:Factor X Deficiency / Q000151:congenital / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003029:Coagulants; D005170:Factor X
keywords: clinical trial; clotting factor concentrate; factor X deficiency; incremental recovery; pharmacokinetics