PMID- 12038784
OWN - NLM
STAT- MEDLINE
DCOM- 20020909
LR  - 20161025
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 87
IP  - 5
DP  - 2002 May
TI  - Pharmacokinetics of recombinant factor IX after intravenous and subcutaneous 
      administration in dogs and cynomolgus monkeys.
PG  - 824-30
AB  - Hemophilia B therapy requires intravenous (IV) infusions of large volumes of 
      factor IX due to the low concentration of factor IX in concentrates 
      (approximately 100 IU/mL). High concentration recombinant factor IX (rFIX) could 
      be a significant advance since it would reduce the large volumes necessary for IV 
      dosing and allow for low-volume subcutaneous (SC) administration. To evaluate 
      high concentration factor IX, we produced formulations with either 2,000 or 4,000 
      IU/mL and studied the SC bioavailability in beagle dogs, cynomolgus monkeys and 
      hemophilia B dogs along with efficacy in hemophilia B dogs. Beagle dog SC 
      bioavailability was 86.4% using a 2000 IU/mL formulation and 77.0% using a 4000 
      IU/mL formulation. Monkey bioavailability of a 4000 IU/mL formulation of rFIX was 
      34.8%. A single SC administration of 200 IU/kg (4000 IU/mL) of rFIX to hemophilia 
      B dogs, produced factor IX clotting activity above 5% for 5 days with a 
      bioavailability of 48.6%. High concentration SC rFIX has an acceptable 
      pharmacokinetic profile in monkeys and dogs, and produces a sustained FIX 
      activity in hemophilic dogs.
FAU - McCarthy, K
AU  - McCarthy K
AD  - Wyeth Research, Cambridge, MA 02140, USA.
FAU - Stewart, P
AU  - Stewart P
FAU - Sigman, J
AU  - Sigman J
FAU - Read, M
AU  - Read M
FAU - Keith, J C Jr
AU  - Keith JC Jr
FAU - Brinkhous, K M
AU  - Brinkhous KM
FAU - Nichols, T C
AU  - Nichols TC
FAU - Schaub, R G
AU  - Schaub RG
LA  - eng
GR  - R24 HL063098/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Recombinant Proteins)
RN  - 9001-28-9 (Factor IX)
SB  - IM
MH  - Animals
MH  - Biological Availability
MH  - Disease Models, Animal
MH  - Dog Diseases/drug therapy
MH  - Dogs
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Factor IX/administration & dosage/*pharmacokinetics/therapeutic use
MH  - Hemophilia B/drug therapy/veterinary
MH  - Injections, Subcutaneous
MH  - Macaca fascicularis
MH  - Male
MH  - Recombinant Proteins/administration & dosage/pharmacokinetics/therapeutic use
MH  - Species Specificity
EDAT- 2002/06/01 10:00
MHDA- 2002/09/11 10:01
CRDT- 2002/06/01 10:00
PHST- 2002/06/01 10:00 [pubmed]
PHST- 2002/09/11 10:01 [medline]
PHST- 2002/06/01 10:00 [entrez]
PST - ppublish
SO  - Thromb Haemost. 2002 May;87(5):824-30.