title: Evaluation of recombinant human factor IX: pharmacokinetic studies in the rat and the dog.
abstract: 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 i.v. doses in dogs, were similar. Peak plasma concentrations of rhFIX and Mononine were 4-5 micrograms/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 i.v., daily) for 28 days or Mononine (40 IU/kg i.v. 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.
authors.affiliation: Department of Preclinical Research, Genetics Institute, Inc., Cambridge, MA 02140, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Keith
authors.forename: T J
authors.initials: TJ
authors.lastname: Ferranti
authors.forename: B
authors.initials: B
authors.lastname: Misra
authors.forename: T
authors.initials: T
authors.lastname: Frederick
authors.forename: B
authors.initials: B
authors.lastname: Rup
authors.forename: K
authors.initials: K
authors.lastname: McCarthy
authors.forename: R
authors.initials: R
authors.lastname: Faulkner
authors.forename: L
authors.initials: L
authors.lastname: Bush
authors.forename: R G
authors.initials: RG
authors.lastname: Schaub
mesh_terms: D000818:Animals; D000917:Antibody Formation; D004285:Dogs; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D005164:Factor IX / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D010865:Pilot Projects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics*; D013045:Species Specificity; D013997:Time Factors
chemical_list: D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C093388:Mononine; D005164:Factor IX