title: Preclinical studies of recombinant factor IX.
abstract: Recombinant factor IX (rFIX) has been extensively evaluated in preclinical studies. Dog model study of hemophilia B indicated that rFIX was as effective as a highly purified plasma-derived replacement factor in normalizing indices of hemostasis. Pharmacokinetic studies indicated a dose-proportional profile for rFIX. Pharmacokinetic/pharmacodynamic analysis showed that increases in the plasma concentration of rFIX following administration were closely correlated with measured factor IX activity in the plasma. Appropriate in vitro and in vivo toxicology studies have been performed to support the clinical use of rFIX for the treatment of hemophilia B. Finally, experiments in a model of thrombogenicity indicated that in animals rFIX has a low thrombogenic potential. The preclinical results provided a basis for proceeding with human clinical trials.
authors.affiliation: Genetics Institute, Inc, Andover, MA 01810, USA.
authors.forename: R
authors.initials: R
authors.lastname: Schaub
authors.forename: P
authors.initials: P
authors.lastname: Garzone
authors.forename: P
authors.initials: P
authors.lastname: Bouchard
authors.forename: B
authors.initials: B
authors.lastname: Rup
authors.forename: J
authors.initials: J
authors.lastname: Keith
authors.forename: K
authors.initials: K
authors.lastname: Brinkhous
authors.forename: G
authors.initials: G
authors.lastname: Larsen
mesh_terms: D000818:Animals; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005164:Factor IX / Q000009:adverse effects / Q000235:genetics / Q000592:standards / Q000627:therapeutic use*; D002836:Hemophilia B / Q000188:drug therapy*; D006801:Humans; D011994:Recombinant Proteins / Q000009:adverse effects / Q000235:genetics / Q000592:standards / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D005164:Factor IX