Abstract | INTRODUCTION: MATERIAL AND METHODS: [(3)H]-rIX-FP, [(3)H]-rFIX or [(3)H]- albumin were administered to rats followed by quantitative whole-body autoradiography over 24 or 240 hours, and the tissue distribution as well as elimination of radioactivity were measured. RESULTS: Elimination of all radioactivity derived from the three proteins was shown to occur primarily via the urine. The tissue distribution of [(3)H]-rIX-FP and [(3)H]-rFIX (but not of [(3)H]- albumin) was comparable, both penetrating predominantly into bone, and well-perfused tissues, suggesting that the rIX moiety determines the distribution pattern of rIX-FP, while the albumin moity is responsible for the prolonged plasma and tissue retention. Detailed knee-joint analysis indicated rapid presence of [(3)H]-rIX-FP and [(3)H]-rFIX in synovial and mineralised bone tissue, mostly localised to the zone of calcified cartilage. Longest retention times were observed in the bone marrow and the endosteum of long bones. Intriguingly, [(3)H]-rIX-FP- and [(3)H]- albumin-derived radioactive signals were detectable up to 240 hours, while [(3)H]-rFIX-derived radioactivity rapidly declined after 1hour post-dosing correlating to the extended plasma half-life of [(3)H]-rIX-FP. CONCLUSION: The prolonged plasma and tissue retention of rIX-FP achieved by albumin fusion may allow a reduction in dosing frequency leading to increased therapeutic compliance and convenience.
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Authors | Eva Herzog, Stephen Harris, Claire Henson, Andrew McEwen, Sabrina Schenk, Marc W Nolte, Ingo Pragst, Gerhard Dickneite, Stefan Schulte, Sabine Zollner |
Journal | Thrombosis research
(Thromb Res)
Vol. 133
Issue 5
Pg. 900-7
(May 2014)
ISSN: 1879-2472 [Electronic] United States |
PMID | 24680550
(Publication Type: Journal Article)
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Copyright | Copyright © 2014. Published by Elsevier Ltd. |
Chemical References |
- Albumins
- Recombinant Fusion Proteins
- Factor IX
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Topics |
- Albumins
(pharmacokinetics)
- Animals
- Factor IX
(pharmacokinetics)
- Humans
- Knee Joint
(metabolism)
- Male
- Rats
- Rats, Sprague-Dawley
- Recombinant Fusion Proteins
(pharmacokinetics)
- Tissue Distribution
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