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Related Experiment Videos

First human studies with a high-molecular-weight iron chelator.

P R Dragsten1, P E Hallaway, G J Hanson

  • 1Biomedical Frontiers Inc, Minneapolis, Minnesota, 55414, USA.

The Journal of Laboratory and Clinical Medicine
|January 19, 2000
PubMed
Summary

A new iron chelator, hydroxyethyl starch-deferoxamine mesylate (HES-DFO), was developed to improve iron chelation therapy. This novel chelator is well tolerated and effectively increases iron excretion in humans.

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Area of Science:

  • Pharmacology
  • Biochemistry
  • Toxicology

Background:

  • Reactive iron release contributes to tissue damage in conditions like ischemia-reperfusion injury.
  • Deferoxamine mesylate (DFO) is an approved iron chelator but has limitations for acute care due to toxicity and short half-life.

Purpose of the Study:

  • To develop and evaluate a novel high-molecular-weight iron chelator, HES-DFO, for improved therapeutic potential.
  • To assess the safety, tolerability, and pharmacokinetic profile of intravenous HES-DFO in healthy male subjects.

Main Methods:

  • Hydroxyethyl starch was chemically coupled to deferoxamine mesylate to create HES-DFO.
  • HES-DFO was administered intravenously to healthy male subjects over 4 hours.
  • Plasma chelator levels, residence time, and urinary iron excretion were measured.

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Main Results:

  • Intravenous HES-DFO was well tolerated, with no observed acute toxicity.
  • Achieved maximum plasma chelator levels (approx. 3 mmol/L) significantly higher than DFO.
  • Demonstrated a prolonged plasma residence time (half-life of 22-33 hours) and markedly stimulated urinary iron excretion (7.1 mg in 48 hours).

Conclusions:

  • Intravenous HES-DFO is a safe and well-tolerated iron chelator in humans.
  • HES-DFO achieves substantial and prolonged plasma concentrations.
  • This novel chelator effectively enhances urinary iron excretion, offering a promising alternative for iron chelation therapy.