Pharmaco/ferrokinetic-related pro-oxidant activity of deferiprone in beta-thalassemia.
The potential of free radical formation in serum of beta-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 (aH=0.18 mT) and DMPO-carbon centred adduct (aH=2.37 mT, aN=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.
Department of Pharmacology, Faculty of Science, Mahidol University, Rajatevee, Bangkok, Thailand.
Totsapol
T
Jirasomprasert
Noppawan P
NP
Morales
Lie M G
LM
Limenta
Srisuporn
S
Sirijaroonwong
Paveena
P
Yamanont
Prapin
P
Wilairat
Suthat
S
Fucharoen
Udom
U
Chantharaksri
D000328:Adult; D003497:Cyclic N-Oxides; D000077543:Deferiprone; D003683:Dehydroascorbic Acid / Q000031:analogs & derivatives / Q000097:blood; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005609:Free Radicals / Q000097:blood; D006801:Humans; D007501:Iron / Q000097:blood; D007502:Iron Chelating Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D008297:Male; D016877:Oxidants / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood* / Q000493:pharmacokinetics; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood* / Q000493:pharmacokinetics; D019097:Spin Trapping; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood* / Q000188:drug therapy*
D003497:Cyclic N-Oxides; D005609:Free Radicals; D007502:Iron Chelating Agents; D016877:Oxidants; D011728:Pyridones; D000077543:Deferiprone; C000820:semidehydroascorbic acid; C017245:5,5-dimethyl-1-pyrroline-1-oxide; D007501:Iron; D003683:Dehydroascorbic Acid