EVALUATION OF RECOMBINANT HUMAN FACTOR-IX - PHARMACOKINETIC STUDIES IN THE RAT AND THE DOG

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(TM), 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(TM) were 4-5 mu g/ml. The mean plasma half-lives were 13.2 +/- 1.6 h for rhFIX and 13.3 +/- 1.6 h for Mononine(TM). Dogs also received rhFIX (40 IU/kg IV, daily) for 28 days or Mononine(TM) (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(TM) (40 IU/kg) dogs.