Recombinant, B-domain deleted factor VIII (r-VIII SQ): pharmacokinetics and initial safety aspects in hemophilia A patients.
The pharmacokinetics of a second-generation recombinant B-domain deleted factor VIII (FVIII) preparation (r-VIII SQ) were studied in 36 patients with severe hemophilia A. In contrast to full-length recombinant FVIII, no albumin needs to be added to stabilize the final formulation of this B-domain deleted FVIII preparation. The in vivo recovery and half-life of r-VIII SQ were similar to those of plasma-derived (pd) FVIII (mean half-life of r-VIII SQ, 11.7 h). The volume of distribution and clearance were slightly, but significantly, higher for r-VIII SQ than for pdFVIII (p < 0.05). Peak plasma levels of FVIII were consistently related to the administered dose of r-VIII SQ (r = 0.94, p < 0.0001). The pharmacokinetic profile of r-VIII SQ remained essentially unchanged in a dose range of 25-100 IU/kg body weight and could be reproduced after repeated doses. r-VIII SQ was well tolerated. In conclusion, deletion of the B-domain of FVIII does not influence its in vivo pharmacokinetics.
Fijnvandraat
K
K
Academic Medical Center, University of Amsterdam, Emma Children's Hospital AMC, The Netherlands.
Berntorp
E
E
ten Cate
J W
JW
Johnsson
H
H
Peters
M
M
Savidge
G
G
Tengborn
L
L
Spira
J
J
Stahl
C
C
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D005169:Factor VIII / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D012449:Safety; D017384:Sequence Deletion; D016037:Single-Blind Method
D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D005169:Factor VIII