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.

PATIENTS/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: C Négrier, C Rothschild, J Goudemand, J Y Borg, S Claeyssens, M C Alessi, A C Jaffry, C Teboul, B Padrazzi, T Waegemans
• Journal: Journal of thrombosis and haemostasis : JTH (J Thromb Haemost) Vol. 6 Issue 9 Pg. 1494-9 (Sep 2008) ISSN: 1538-7836 [Electronic] England
• PMID: 18627444 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Fibrinogen

Topics

• Adult
• Afibrinogenemia (drug therapy)
• Aged
• Area Under Curve
• Fibrinogen (adverse effects, analysis, pharmacokinetics, pharmacology, therapeutic use)
• Half-Life
• Humans
• Middle Aged