Pharmaco/ferrokinetic-related pro-oxidant activity of deferiprone in β-thalassemia

• Published in: Free radical research Vol. 43; no. 5; pp. 485 - 491
• Main Authors: Jirasomprasert, Totsapol, Morales, Noppawan P., Limenta, Lie M. G., Sirijaroonwong, Srisuporn, Yamanont, Paveena, Wilairat, Prapin, Fucharoen, Suthat, Chantharaksri, Udom
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 2009
• Subjects: Adult; Ascorbyl radical; beta-thalassemia; beta-Thalassemia - blood; beta-Thalassemia - drug therapy; Cyclic N-Oxides; deferiprone; Dehydroascorbic Acid - analogs & derivatives; Dehydroascorbic Acid - blood; Electron Spin Resonance Spectroscopy; EPR; Female; Free Radicals - blood; Humans; Iron - blood; Iron Chelating Agents - administration & dosage; Iron Chelating Agents - adverse effects; Iron Chelating Agents - pharmacokinetics; Male; Oxidants - administration & dosage; Oxidants - adverse effects; Oxidants - blood; Oxidants - pharmacokinetics; pro-oxidant; Pyridones - administration & dosage; Pyridones - adverse effects; Pyridones - blood; Pyridones - pharmacokinetics; Spin Trapping; Young Adult
• ISSN: 1071-5762; 1029-2470
• DOI: 10.1080/10715760902870611

The potential of free radical formation in serum of β-thalassemia/Hb E patients receiving a single oral dose of 25 mg/kg body weight of deferiprone, a bidentate orally active iron chelator, was evaluated using EPR/spin trapping technique. In the presence of ascorbic acid and tert-butylhydroperoxide, EPR signals of ascorbyl radical (a H =0.18 mT) and DMPO-carbon centred adduct (a H =2.37 mT, a N =1.65 mT) were detected. Shortly after deferiprone administration, EPR signal intensities decreased concomitant with an increase in serum levels of deferiprone. Unfortunately, enhanced EPR signal intensities were observed at 300 min after dosing in patients with serum molar ratio of deferiprone to iron less than 3, suggesting the formation of incomplete iron-deferiprone complexes and consequently free radical formation. To avoid adverse effects of deferiprone, a dosage regimen should be designed according to iron status of the patients and aimed at maintaining an adequate ratio of serum chelator-to-iron concentration.