title: Pharmacokinetics and safety of plasma-derived factor XIII concentrate (human) in patients with congenital factor XIII deficiency.
abstract: Congenital factor XIII (FXIII) deficiency is a rare condition with substantial risk for life-threatening bleeding. Replacement of deficient FXIII with plasma-derived FXIII concentrate is a treatment option. The current 12-week study evaluated the steady-state pharmacokinetic (PK) and safety profile of prophylactic infusions of FXIII concentrate (human) in patients with congenital FXIII deficiency. Patients received FXIII concentrate (human) 40 IU kg(-1) on Days 0, 28, and 56. FXIII levels were assessed before and after each infusion; steady-state PK parameters were assessed up to 28 days after the infusion on Day 56. Treatment effectiveness in maintaining trough FXIII activity levels ≥ 5% over 28 days and safety parameters were also assessed. Fourteen patients received FXIII concentrate (human) and 13 completed the study. Post-infusion, FXIII activity levels increased to within the range found in patients without congenital FXIII deficiency without reaching supra-therapeutic levels. Non-baseline-adjusted trough FXIII activity levels were maintained at or above 10% at all post-baseline visits in all patients. Steady-state PK parameters were baseline-adjusted; maximum FXIII activity was 87.7% at 1.72 h post-infusion, subsequently declining to a minimum of 5.0%. The half-life was 6.6 days. FXIII concentrate (human) was generally well tolerated. Two patients had possibly treatment-related adverse events. There were no reports of thromboembolism, viral transmission, bleeding events or treatment-related hypersensitivity. These findings support use of FXIII concentrate (human) 40 IU kg(-1) every 28 days as an appropriate regimen for routine, long-term prophylaxis in children and adults with congenital FXIII deficiency.
  
  
  BACKGROUND
  www.clinicaltrials.gov/ct2/show/NCT00883090.
authors.affiliation: Children's Hospital of Orange County (CHOC), Orange, CA, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Nugent
authors.forename: C
authors.initials: C
authors.lastname: Ashley
authors.forename: J
authors.initials: J
authors.lastname: García-Talavera
authors.forename: L C
authors.initials: LC
authors.lastname: Lo
authors.forename: A S
authors.initials: AS
authors.lastname: Mehdi
authors.forename: A
authors.initials: A
authors.lastname: Mangione
mesh_terms: D000293:Adolescent; D000328:Adult; D054316:Biomarkers, Pharmacological; D002648:Child; D002675:Child, Preschool; D005176:Factor XIII / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005177:Factor XIII Deficiency / Q000151:congenital* / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D054316:Biomarkers, Pharmacological; D005176:Factor XIII
keywords: bleeding disorders; coagulation; congenital factor XIII deficiency; factor XIII; pharmacokinetics; prophylaxis