Pharmacokinetics of monoclonally-purified and recombinant factor VIII in patients with severe von Willebrand disease.
A monoclonally-purified factor VIII (FVIII) concentrate, containing little von Willebrand factor (vWF), was infused to 11 patients with severe von Willebrand disease and unmeasurable levels of plasma vWF. In comparison with the historical data obtained infusing hemophiliacs in the same conditions, monoclonally-purified FVIII had a significantly shorter half-life and faster clearance from plasma but similar in vivo recovery and volume of distribution. Two additional patients with severe von Willebrand disease were also infused with recombinant FVIII totally devoid of vWF. Half-life was very short and in vivo recovery low, with a larger volume of distribution than for monoclonally-purified FVIII. We conclude that in patients with severe von Willebrand disease the small amounts of vWF contained in the monoclonally-purified FVIII concentrate are not sufficient to stabilize infused FVIII, nor to support the normal circulation of endogenous FVIII that these patients produce at a normal rate.
Morfini
M
M
Hematology Department, University of Florence, Italy.
Mannucci
P M
PM
Tenconi
P M
PM
Longo
G
G
Mazzucconi
M G
MG
Rodeghiero
F
F
Ciavarella
N
N
De Rosa
V
V
Arter
A
A
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001825:Body Fluid Compartments; D005169:Factor VIII / Q000276:immunology / Q000302:isolation & purification / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D014842:von Willebrand Diseases / Q000097:blood / Q000628:therapy*; D014841:von Willebrand Factor / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D005169:Factor VIII