Pharmacokinetics and tissue distribution of deferoxamine-based nanochelator in rats
Aim: To characterize the pharmacokinetics of deferoxamine-conjugated nanoparticles (DFO-NPs), a novel nanochelator for removing excess iron. Materials & methods: The pharmacokinetics of DFO-NPs were evaluated in Sprague-Dawley rats at three doses (3.3, 10 and 30 μmol/kg) after intravenous and subcutaneous administration. Results: DFO-NPs exhibited a biphasic concentration-time profile after intravenous administration with a short terminal half-life (2.0-3.2 h), dose-dependent clearance (0.111-0.179 l/h/kg), minimal tissue distribution and exclusive renal excretion with a possible saturable reabsorption mechanism. DFO-NPs after subcutaneous administration exhibited absorption-rate-limited kinetics with a prolonged half-life (5.7-10.1 h) and favorable bioavailability (47-107%). Conclusion: DFO-NPs exhibit nonlinear pharmacokinetics with increasing dose, and subcutaneous administration substantially improves drug exposure, thereby making it a clinically viable administration route for iron chelation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Nanomedicine (London, England) - 17(2022), 22 vom: 18. Sept., Seite 1649-1662 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jones, Gregory [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.01.2023 Date Revised 20.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.2217/nnm-2022-0159 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM350587752 |
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| 245 | 1 | 0 | |a Pharmacokinetics and tissue distribution of deferoxamine-based nanochelator in rats |
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| 500 | |a Date Revised 20.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: To characterize the pharmacokinetics of deferoxamine-conjugated nanoparticles (DFO-NPs), a novel nanochelator for removing excess iron. Materials & methods: The pharmacokinetics of DFO-NPs were evaluated in Sprague-Dawley rats at three doses (3.3, 10 and 30 μmol/kg) after intravenous and subcutaneous administration. Results: DFO-NPs exhibited a biphasic concentration-time profile after intravenous administration with a short terminal half-life (2.0-3.2 h), dose-dependent clearance (0.111-0.179 l/h/kg), minimal tissue distribution and exclusive renal excretion with a possible saturable reabsorption mechanism. DFO-NPs after subcutaneous administration exhibited absorption-rate-limited kinetics with a prolonged half-life (5.7-10.1 h) and favorable bioavailability (47-107%). Conclusion: DFO-NPs exhibit nonlinear pharmacokinetics with increasing dose, and subcutaneous administration substantially improves drug exposure, thereby making it a clinically viable administration route for iron chelation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a absorption-rate limited kinetics | |
| 650 | 4 | |a iron chelator | |
| 650 | 4 | |a nonlinear pharmacokinetics | |
| 650 | 4 | |a renal clearance | |
| 650 | 4 | |a saturable reabsorption | |
| 650 | 7 | |a Deferoxamine |2 NLM | |
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| 650 | 7 | |a Iron Chelating Agents |2 NLM | |
| 700 | 1 | |a Zeng, Lingxue |e verfasserin |4 aut | |
| 700 | 1 | |a Stiles, Wesley R |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Seung Hun |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Homan |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Hak Soo |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Jonghan |e verfasserin |4 aut | |
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