Pharmacokinetic studies on Wilfactin(R), a von Willebrand factor concentrate with a low factor VIII content treated with three virus-inactivation/removal methods.
GOUDEMAND, J. *; SCHARRER, I. +; BERNTORP, E. ++; LEE, C. A. [S]; BOREL-DERLON, A. [P]; STIELTJES, N. **; CARON, C. *; SCHERRMANN, J. M. ++; BRIDEY, F. ++++; TELLIER, Z. ++++; FEDERICI, A. B. [S][S]; MANNUCCI, P. M. [S][S]
[Article]
Journal of Thrombosis & Haemostasis.
3(10):2219-2227, October 2005.
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Objective: In order to correct the primary von Willebrand factor (VWF) defect and avoid supra-physiologic plasma levels of factor VIII, a pure VWF concentrate almost devoid of FVIII was developed and used in France since 1989.
Methods: The pharmacokinetic (PK) profile of the most recent version of this concentrate (Wilfactin(R); LFB, Les Ulis, France), treated with three virus-inactivation/removal methods (solvent/detergent, 35 nm filtration, dry heat treatment), was investigated in 25 patients. Seventeen patients with various types of clinically severe von Willebrand disease (VWD) were included in a crossover, randomized trial carried out in five European centers and comparing Wilfactin(R) with concentrates containing both FVIII and VWF (FVIII/VWF). Eight type 3 VWD patients were included in another trial carried out in six French centers comparing Wilfactin(R) with its previous version (Facteur Willebrand-LFB(R); LFB) that adopted one virus-inactivation method only.
Results: For both the measurements evaluated in this study (VWF antigen, VWF:Ag; and VWF ristocetin co-factor activity, VWF:RCo), Wilfactin(R) had a PK profile similar to that of the FVIII/VWF concentrates and of Facteur Willebrand-LFB(R). VWF:RCo and VWF:Ag recoveries were 2.1 /- 0.3 and 1.8 /- 0.3 per IU kg-1, respectively, and the half-lives were 12.4 /- 1.8 and 15.9 /- 1.5 h. The FVIII synthesis rate was 5.8 /- 1.0 IU dL-1 h-1, with a half-life of 15.8 /- 2.4 h.
Conclusion: The PK of VWF and FVIII have not been altered by the three virus-inactivation/removal steps during the manufacturing of Wilfactin(R).
Copyright (C) 2005 Blackwell Publishing Ltd.
