Pharmacokinetic studies on Wilfactin, a von Willebrand factor concentrate with a low factor VIII content treated with three virus-inactivation/removal methods.
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.


CONCLUSIONS
The PK of VWF and FVIII have not been altered by the three virus-inactivation/removal steps during the manufacturing of Wilfactin.
Goudemand
J
J
Haematology Institute, University Hospital, Lille, France. j-goudemand@chru-lille.fr
Scharrer
I
I
Berntorp
E
E
Lee
C A
CA
Borel-Derlon
A
A
Stieltjes
N
N
Caron
C
C
Scherrmann
J M
JM
Bridey
F
F
Tellier
Z
Z
Federici
A B
AB
Mannucci
P M
PM
D000328:Adult; D000368:Aged; D001780:Blood Coagulation Tests; D003257:Consumer Product Safety; D005169:Factor VIII / Q000096:biosynthesis / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010599:Pharmacokinetics; D013242:Sterilization / Q000379:methods*; D038301:Virus Inactivation; D014842:von Willebrand Diseases / Q000188:drug therapy*; D014841:von Willebrand Factor / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
D014841:von Willebrand Factor; D005169:Factor VIII