title: Pharmacokinetics of recombinant factor XIII at steady state in patients with congenital factor XIII A-subunit deficiency.
abstract: BACKGROUND
  The use of monthly recombinant factor XIII (rFXIII) recently demonstrated favorable safety and efficacy for congenital FXIII A-subunit deficiency patients aged ≥ 6 years (mentor(™) 1 trial), although the pharmacokinetics (PK) were not fully evaluated.
  
  
  OBJECTIVE
  To comprehensively evaluate the steady-state PK of rFXIII in patients aged ≥ 6 years with congenital FXIII A-subunit deficiency.
  
  
  METHODS
  mentor(™) 2 is an ongoing, multinational safety and efficacy trial in which patients are receiving monthly rFXIII (35 IU kg(-1) ) for ≥ 52 weeks. For this 28-day PK analysis, blood samples were collected immediately predosing, and 1 h, 2 h, 3, 7, 14, 21, and 28 days postdosing. FXIII activity was measured and PK parameters were calculated using non-compartmental analysis, without prior baseline adjustment. Information regarding adverse events and bleeding was collected at each visit. Antibody assessments were performed predosing and at day 28.
  
  
  RESULTS
  PK analysis in 23 patients revealed first-order elimination of rFXIII with a geometric mean half-life of 13.6 days. Mean FXIII activity was > 0.1 IU mL(-1) throughout the 28-day period, with a geometric mean peak activity of 0.87 IU mL(-1) and trough of 0.16 IU mL(-1) . The geometric mean clearance was 0.15 mL h(-1) kg(-1) . No bleeding episodes occurred during the PK session, and no anti-rFXIII antibodies were detected. Peak and trough FXIII activities were constant over time, compared with previous activities (≥ 10 rFXIII doses) in the same patients.
  
  
  CONCLUSIONS
  Clearance of rFXIII is unaffected over time, and monthly prophylaxis with 35 IU kg(-1) rFXIII provides FXIII activity > 0.1 IU mL(-1) throughout the dosing interval in patients with congenital FXIII A-subunit deficiency.
authors.affiliation: Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, OH, USA.
authors.forename: B
authors.initials: B
authors.lastname: Kerlin
authors.forename: B
authors.initials: B
authors.lastname: Brand
authors.forename: A
authors.initials: A
authors.lastname: Inbal
authors.forename: S
authors.initials: S
authors.lastname: Halimeh
authors.forename: D
authors.initials: D
authors.lastname: Nugent
authors.forename: M
authors.initials: M
authors.lastname: Lundblad
authors.forename: R
authors.initials: R
authors.lastname: Tehranchi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000032:analysis; D019540:Area Under Curve; D002648:Child; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005177:Factor XIII Deficiency / Q000097:blood / Q000188:drug therapy*; D026122:Factor XIIIa / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013997:Time Factors; D055815:Young Adult
chemical_list: D000906:Antibodies; D011994:Recombinant Proteins; D026122:Factor XIIIa
keywords: factor XIII; factor XIII deficiency; fibrinolysis; pharmacokinetics; recombinant factor XIII-A2