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Pharmacokinetics and pharmacodynamics of a new highly secured fibrinogen concentrate
Author(s) -
NÉGRIER C.,
ROTHSCHILD C.,
GOUDEMAND J.,
BORG J. Y.,
CLAEYSSENS S.,
ALESSI M. C.,
JAFFRY A. C.,
TEBOUL C.,
PADRAZZI B.,
WAEGEMANS T.
Publication year - 2008
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2008.03076.x
Subject(s) - pharmacodynamics , pharmacokinetics , fibrinogen , pharmacology , medicine
Summary. 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.