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Thromb Haemost 1997; 77(02): 298-302
DOI: 10.1055/s-0038-1655957
Original Article
Schattauer GmbH Stuttgart

Recombinant, B-domain Deleted Factor VIII (r-VIII SQ): Pharmacokinetics and Initial Safety Aspects in Hemophilia A Patients

K Fijnvandraat
1   The Academic Medical Center, University of Amsterdam, Emma Children’s Hospital AMC, Department of Pediatrics, Amsterdam, The Netherlands
2   Center for Thrombosis, Hemostasis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands
,
E Berntorp
3   Malmø University Hospital, Malmø, Sweden
,
J W ten Cate
2   Center for Thrombosis, Hemostasis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands
,
H Johnsson
4   Karolinska Hospital, Stockholm, Sweden
,
M Peters
1   The Academic Medical Center, University of Amsterdam, Emma Children’s Hospital AMC, Department of Pediatrics, Amsterdam, The Netherlands
,
G Savidge
5   St. Thomas Hospital, London, United Kingdom
,
L Tengborn
6   Sahlgrenska Hospital, Göteborg, Sweden
,
J Spira
7   Pharmacia AB, Stockholm, Sweden
,
C Stahl
7   Pharmacia AB, Stockholm, Sweden
› Author Affiliations
Further Information

Publication History

Received 25 June 1996

Accepted after revision 09 October 1996

Publication Date:
10 July 2018 (online)

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Summary

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.

 

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