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

K Fijnvandraat; E Berntorp; J W ten Cate; H Johnsson; M Peters; G Savidge; L Tengborn; J Spira; C Stahl

doi:10.1055/s-0038-1655957

Thrombosis and Haemostasis, Table of Contents

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

¹The Academic Medical Center, University of Amsterdam, Emma Children’s Hospital AMC, Department of Pediatrics, Amsterdam, The Netherlands

²Center for Thrombosis, Hemostasis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands

,

E Berntorp

³Malmø University Hospital, Malmø, Sweden

,

J W ten Cate

²Center for Thrombosis, Hemostasis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam, The Netherlands

,

H Johnsson

⁴Karolinska Hospital, Stockholm, Sweden

,

M Peters

¹The Academic Medical Center, University of Amsterdam, Emma Children’s Hospital AMC, Department of Pediatrics, Amsterdam, The Netherlands

,

G Savidge

⁵St. Thomas Hospital, London, United Kingdom

,

L Tengborn

⁶Sahlgrenska Hospital, Göteborg, Sweden

,

J Spira

⁷Pharmacia AB, Stockholm, Sweden

,

C Stahl

⁷Pharmacia AB, Stockholm, Sweden

› Author Affiliations

Abstract

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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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References

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