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®; 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® 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® with its previous version (Facteur Willebrand-LFB®; 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® had a PK profile similar to that of the FVIII/VWF concentrates and of Facteur Willebrand-LFB®. 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®.
Pharmacokinetic studies on Wilfactin((R)), a von Willebrand factor concentrate with a low factor VIII content treated with three virus-inactivation/removal methods / J. Goudemand, I. Scharrer, E. Berntorp, C.A. Lee, A. Borel-Derlon, N. Stieltjes, C. Caron, J.M. Scherrmann, F. Bridey, Z. Tellier, A.B. Federici, P.M. Mannucci. - In: JOURNAL OF THROMBOSIS AND HAEMOSTASIS. - ISSN 1538-7933. - 3:10(2005), pp. 2219-2227.
|Titolo:||Pharmacokinetic studies on Wilfactin((R)), a von Willebrand factor concentrate with a low factor VIII content treated with three virus-inactivation/removal methods|
FEDERICI, AUGUSTO BRAMANTE (Penultimo)
MANNUCCI, PIER MANNUCCIO (Ultimo)
|Parole Chiave:||pharmacokinetic; severe von Willebrand disease; viral safety; von Willebrand factor concentrate|
|Settore Scientifico Disciplinare:||Settore MED/15 - Malattie del Sangue|
Settore MED/09 - Medicina Interna
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1538-7836.2005.01435.x|
|Appare nelle tipologie:||01 - Articolo su periodico|