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Thromb Haemost 2001; 85(03): 445-449
DOI: 10.1055/s-0037-1615602
Review Article
Schattauer GmbH

Intratracheal Administration of Recombinant Human Factor IX (BeneFix™) Achieves Therapeutic Levels in Hemophilia B Dogs

K. E. Russell
1   Departments of Pathology and Laboratory Medicine
,
M. S. Read
1   Departments of Pathology and Laboratory Medicine
,
D. A. Bellinger
1   Departments of Pathology and Laboratory Medicine
,
K. Leitermann
3   Genetics Institute, Inc., Andover, Massachusetts, USA
,
B. J. Rup
3   Genetics Institute, Inc., Andover, Massachusetts, USA
,
K. P. McCarthy
3   Genetics Institute, Inc., Andover, Massachusetts, USA
,
J. C. Keith Jr.
3   Genetics Institute, Inc., Andover, Massachusetts, USA
,
S. P. Khor
3   Genetics Institute, Inc., Andover, Massachusetts, USA
,
R. G. Schaub
3   Genetics Institute, Inc., Andover, Massachusetts, USA
,
T. C. Nichols
1   Departments of Pathology and Laboratory Medicine
2   Medicine University of North Carolina, Chapel Hill, North Carolina
› Author Affiliations
Further Information

Publication History

Received 04 July 2000

Accepted after revision 12 September 2000

Publication Date:
08 December 2017 (online)

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Summary

The purpose of this paper was to establish proof of concept for administration of human recombinant F.IX (rF.IX) by inhalation for therapy of hemophilia B. The pharmacokinetics of intratracheal (IT) administration of rF.IX was studied in nine hemophilia B dogs randomized into 3 groups that received 200 IU/kg IT, 1000 IU/kg IT, or 200 IU/kg intravenously (IV). IT rF.IX produced therapeutic levels of F.IX antigen and activity and the pharmacokinetic parameters were consistent with a slow release from a depot site within the lungs. Bio-availability compared to IV administration was 11% for 200 IU/kg IT and 4.9% for 1000 IU/kg. The whole blood clotting time began to shorten at 2 h but F.IX bioactivity was not detected until 8 h post infusion in both IT groups. In all groups, F.IX activity was detected through 72 h post administration. These data demonstrate that biologically active rF.IX can reach the systemic circulation when given IT. Aerosolization of rF.IX may provide a needle-free therapeutic option for delivery of rF.IX to hemophilia B patients.

Key words

Factor IX - hemophilia B - inhalation therapy
 

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