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Pharmacokinetics and tissue distribution of deferoxamine-based nanochelator in rats supplementary dataset

dataset
posted on 2022-12-22, 14:57 authored by Gregory Jones, Lingxue Zeng, Wesley R Stiles, Seung Hun Park, Homan Kang, Hak Soo Choi, Jonghan Kim

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.

Funding

National Heart, Lung, and Blood Institute, (Grant / Award Number: 'HL143020')

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