title: Pharmacokinetics and pharmacodynamics of a new highly secured fibrinogen concentrate.
abstract: BACKGROUND
  Inherited afibrinogenemia is a rare autosomal recessive disorder characterized by the absence or trace amounts of plasma fibrinogen inducing varying bleeding tendencies. Little is known about the pharmacokinetics of plasma-derived fibrinogen concentrates used in the treatment of afibrinogenemic patients.
  
  
  OBJECTIVE
  This open, prospective, multicenter study assessed the pharmacokinetic and pharmacodynamic profiles of FIBRINOGENE T1 (FGT1; LFB, Les Ulis, France), a human fibrinogen concentrate treated with three specific biological safety steps.
  
  
  METHODS
  Five adult patients with congenital afibrinogenemia received a single infusion of 0.06 g kg(-1) of FGT1. Plasma samples drawn up to day 14 were assayed for fibrinogen antigen and activity and for coagulation parameters in a central laboratory.
  
  
  RESULTS
  Fibrinogen antigen and activity were similar and highly correlated, with very low between-patient variability for pharmacokinetic parameters. Fibrinogen levels increased rapidly and significantly, with a mean plasma concentration of 1.39 g L(-1) being achieved 1 h after the end of the infusion, leading to almost complete in vivo recovery (94%). The mean half-life was 3.4 days, with slow linear elimination, and the distribution was mainly restricted to the vascular compartment. Coagulation parameters were normalized after the infusion and during the following 6-10 days. FGT1 was well tolerated overall.
  
  
  CONCLUSIONS
  FGT1 behaves like natural functional fibrinogen, and its pharmacokinetic properties are in line with those expected from a fibrinogen concentrate. Our findings suggest that FGT1 can restore efficient hemostasis in afibrinogenemic patients, and predict good clinical efficacy.
authors.affiliation: Haemophilia Treatment Centre, Edouard Herriot Hospital, University Claude Bernard Lyon 1, Lyon, France. claude.negrier@chu-lyon.fr
authors.forename: C
authors.initials: C
authors.lastname: Négrier
authors.forename: C
authors.initials: C
authors.lastname: Rothschild
authors.forename: J
authors.initials: J
authors.lastname: Goudemand
authors.forename: J Y
authors.initials: JY
authors.lastname: Borg
authors.forename: S
authors.initials: S
authors.lastname: Claeyssens
authors.forename: M C
authors.initials: MC
authors.lastname: Alessi
authors.forename: A C
authors.initials: AC
authors.lastname: Jaffry
authors.forename: C
authors.initials: C
authors.lastname: Teboul
authors.forename: B
authors.initials: B
authors.lastname: Padrazzi
authors.forename: T
authors.initials: T
authors.lastname: Waegemans
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000188:drug therapy; D000368:Aged; D019540:Area Under Curve; D005340:Fibrinogen / Q000009:adverse effects / Q000032:analysis / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D008875:Middle Aged
chemical_list: D005340:Fibrinogen