Jc. Keith et al., EVALUATION OF RECOMBINANT HUMAN FACTOR-IX - PHARMACOKINETIC STUDIES IN THE RAT AND THE DOG, Thrombosis and haemostasis, 73(1), 1995, pp. 101-105
The pharmacokinetics of intravenously administered recombinant human f
actor 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 fou
nd in only 1 of 12 rats. The pharmacokinetic profiles of rhFIX or Mono
nine(TM), a purified human plasma-derived factor IX, after single 100
IU/kg IV doses in dogs, were similar. Peak plasma concentrations of rh
FIX 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 al
so 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 leve
ls were determined for each compound. Pharmacokinetic half-lives decre
ased in these treated dogs which developed antihuman Factor IX antibod
ies. The antibody responses in 28 day rhFIX (40 IU/kg) dogs were simil
ar to 14 day Mononine(TM) (40 IU/kg) dogs.