Recombinant, B-domain deleted factor VIII (r-VIII SQ) : pharmacokinetics and initial safety aspects in hemophilia A patients
Fijnvandraat, K.; Berntorp, E.; ten Cate, J.W.; Johnsson, H.; Peters, M.; Savidge, G.; Tengborn, L.; Spira, J.; Stahl, C.
Thrombosis and Haemostasis 77(2): 298-302
1997
ISSN/ISBN: 0340-6245 PMID: 9157585 Document Number: 482774
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-VIH SQ than for pdFVIII (p lt 0.05). Peak plasma levels of FVIII were consistently related to the administered dose of r-VIII SQ (r=0.94, p lt 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.