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 delet ed factor VIII (FVIII) preparation (r-VIII SQ) were studied in 36 pati ents 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) FV III (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 t han for pdFVIII (p<0.05). Peak plasma levels of FVIII were consistentl y related to the administered dose of r-VIII SQ (r=0.94, p<0.0001). Th e pharmacokinetic profile of r-VIII SQ remained essentially unchanged in a dose range of 25-100 IU/kg body weight and could be reproduced af ter repeated doses. r-VIII SQ was well tolerated. In conclusion, delet ion of the B-domain of FVIII does not influence its in vivo pharmacoki netics.