Evaluation of Recombinant Human Factor IX: Pharmacokinetic Studies in the Rat and the Dog

James C Keith Jr; Thomas J Ferranti; Bibhu Misra; Thomas Frederick; Bonita Rup; Kyle McCarthy; Robert Faulkner; Larry Bush; Robert G Schaub

doi:10.1055/s-0038-1653732

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1995; 73(01): 101-105
DOI: 10.1055/s-0038-1653732

Original Article

Coagulation

Schattauer GmbH Stuttgart

Evaluation of Recombinant Human Factor IX: Pharmacokinetic Studies in the Rat and the Dog

Authors

James C Keith Jr

The Departments of Preclinical Research and Development, Genetics Institute, Inc., Cambridge, MA, USA
Thomas J Ferranti

The Departments of Preclinical Research and Development, Genetics Institute, Inc., Cambridge, MA, USA
Bibhu Misra

The Departments of Preclinical Research and Development, Genetics Institute, Inc., Cambridge, MA, USA
Thomas Frederick

The Departments of Preclinical Research and Development, Genetics Institute, Inc., Cambridge, MA, USA
Bonita Rup

The Departments of Preclinical Research and Development, Genetics Institute, Inc., Cambridge, MA, USA
Kyle McCarthy

The Departments of Preclinical Research and Development, Genetics Institute, Inc., Cambridge, MA, USA
Robert Faulkner

The Departments of Preclinical Research and Development, Genetics Institute, Inc., Cambridge, MA, USA
Larry Bush

¹The Department of Formulation Process Development, Genetics Institute, Inc., Cambridge, MA, USA
Robert G Schaub

The Departments of Preclinical Research and Development, Genetics Institute, Inc., Cambridge, MA, USA

Abstract

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Summary

The pharmacokinetics of intravenously administered recombinant human factor IX (rhFIX) were studied in Sprague-Dawley rats and Beagle dogs. Rats received rhFIX (50 IU/kg once daily) for 28 days, and the plasma half-life was 5 h. Anti-Human Factor IX serum antibody levels were found in only 1 of 12 rats. The pharmacokinetic profiles of rhFIX or Mononine™, a purified human plasma-derived factor IX, after single 100 IU/kg IV doses in dogs, were similar. Peak plasma concentrations of rhFIX and Mononine™ were 4–5 μg/ml. The mean plasma half-lives were 13.2 ± 1.6 h for rhFIX and 13.3 ± 1.6 h for Mononine™. Dogs also received rhFIX (40 IU/kg IV, daily) for 28 days or Mononine™ (40 IU/kg IV daily) for 14 days. Anti-human Factor IX serum antibody levels were determined for each compound. Pharmacokinetic half-lives decreased in these treated dogs which developed antihuman Factor IX antibodies. The antibody responses in 28 day rhFIX (40 IU/kg) dogs were similar to 14 day Mononine™ (40 IU/kg) dogs.

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References

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