Pharmacokinetics and pharmacodynamics of a new highly secured fibrinogen concentrate.
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.
Négrier
C
C
Haemophilia Treatment Centre, Edouard Herriot Hospital, University Claude Bernard Lyon 1, Lyon, France. claude.negrier@chu-lyon.fr
Rothschild
C
C
Goudemand
J
J
Borg
J Y
JY
Claeyssens
S
S
Alessi
M C
MC
Jaffry
A C
AC
Teboul
C
C
Padrazzi
B
B
Waegemans
T
T
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
D005340:Fibrinogen