Urinary iron excretion in thalassaemia after desferrioxamine administration

Seshadri, R.; Colebatch, John H.; Fisher, Richard H.

doi:10.1136/adc.49.3.195

Cited by 7 publications

(4 citation statements)

References 15 publications

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“…The 4 patients (Cases 5,7,9,and 10) in whom a marked decrease in the amount of urinary iron was observed had undergone splenectomy 3 to 6 months before retesting. We have previously shown that DFAinduced urinary iron excretion decreases markedly after splenectomy (Seshadri, Colebatch, and Fisher, 1974).…”

Section: Resultsmentioning

confidence: 93%

“…Moreover, when assessing the effectiveness of DFA, allowance has to be made for factors such as age, degree of anaemia (Fielding, 1970), and splenectomy (Seshadri et al, 1974) which influence the amount of iron excretion. Our earlier observations on DFA-induced urinary iron excretion suggested that DFA may not be effective in removing the excess iron from the myocardium and liver in the presence of a large spleen (Seshadri et al, 1974).…”

Section: Resultsmentioning

confidence: 99%

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Long-term administration of desferrioxamine in thalassaemia major

Seshadri¹,

Colebatch²,

Gordon³

et al. 1974

Archives of Disease in Childhood

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(1974). Archives of Disease in Childhood, 49,621. Long-term administration of desferrioxamine in thalassaemia major. Studies of desferrioxamine (DFA) as a specific iron-chelating agent in the treatment of haemosiderosis have been reported in various conditions, but there has been only limited evaluation of its long-term use in thalassaemia major. In the present study 1 g DFA was given intramuscularly daily 6 days per week in 3 patients for 5 to 8 years, and in another 7 patients for 10 to 22 months. In addition, 500 mg DFA was added to each unit of donor blood at the time of transfusions. Urinary iron excretion after DFA was estimated using atomic absorption spectrophotometry both before and periodically during DFA treatment. During follow-up, cardiac and liver functions were assessed by ECG, chest x-ray, and liver function tests.The results show that DFA therapy increased urinary iron excretion, and that this was associated with a significant improvement in the clinical symptoms and signs of haemosiderosis and with return towards normal in the ECG and liver function tests.

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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Long-term administration of desferrioxamine in thalassaemia major

Seshadri¹,

Colebatch²,

Gordon³

et al. 1974

Archives of Disease in Childhood

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“…The successful first application of the chelating drug DF for the removal of iron and the treatment of iron overload in TM became a reality. However, the success was limited and short-lived because of the copious administration procedure and the low efficacy of the daily intramuscular injections of DF initially used [90,91]. A substantial improvement in iron excretion was observed following long-term administration, e.g., 24 h intravenous infusion of DF in comparison to its bolus administration [92,93].…”

Section: [C] Clinical and Biological Effectsmentioning

confidence: 99%

“…All three chelating drugs have exceeded the patent restriction period and are classified as generic pharmaceuticals and belong to the orphan drug category [62]. Deferoxamine has been used parenterally for the treatment of iron-overloading conditions for more than 60 years [89][90][91][92][93][94]. Oral L1 was approved by the regulatory authorities of India in 1995, in Europe and in other countries in 1999 and in the USA in 2011 [112,139].…”

Section: The Aim Of Iron Chelation Therapy In Thalassemia and The Des...mentioning

confidence: 99%

Drug Selection and Posology, Optimal Therapies and Risk/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs

Kontoghiorghes

2023

IJMS

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The design of clinical protocols and the selection of drugs with appropriate posology are critical parameters for therapeutic outcomes. Optimal therapeutic protocols could ideally be designed in all diseases including for millions of patients affected by excess iron deposition (EID) toxicity based on personalised medicine parameters, as well as many variations and limitations. EID is an adverse prognostic factor for all diseases and especially for millions of chronically red-blood-cell-transfused patients. Differences in iron chelation therapy posology cause disappointing results in neurodegenerative diseases at low doses, but lifesaving outcomes in thalassemia major (TM) when using higher doses. In particular, the transformation of TM from a fatal to a chronic disease has been achieved using effective doses of oral deferiprone (L1), which improved compliance and cleared excess toxic iron from the heart associated with increased mortality in TM. Furthermore, effective L1 and L1/deferoxamine combination posology resulted in the complete elimination of EID and the maintenance of normal iron store levels in TM. The selection of effective chelation protocols has been monitored by MRI T2* diagnosis for EID levels in different organs. Millions of other iron-loaded patients with sickle cell anemia, myelodysplasia and haemopoietic stem cell transplantation, or non-iron-loaded categories with EID in different organs could also benefit from such chelation therapy advances. Drawbacks of chelation therapy include drug toxicity in some patients and also the wide use of suboptimal chelation protocols, resulting in ineffective therapies. Drug metabolic effects, and interactions with other metals, drugs and dietary molecules also affected iron chelation therapy. Drug selection and the identification of effective or optimal dose protocols are essential for positive therapeutic outcomes in the use of chelating drugs in TM and other iron-loaded and non-iron-loaded conditions, as well as general iron toxicity.

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TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo

Kalanaky¹,

Hafizi

Safari³

et al. 2016

Int J Hematol

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Iron chelation therapy is an effective approach to the treatment of iron overload conditions, in which iron builds up to toxic levels in the body and may cause organ damage. Treatments using deferoxamine, deferasirox and deferiprone have been introduced and despite their disadvantages, they remain the first-line therapeutics in iron chelation therapy. Our study aimed to compare the effectiveness of the iron chelation agent TLc-A, a nano chelator synthetized based on the novel nanochelating technology, with deferoxamine. We found that TLc-A reduced iron overload in Caco2 cell line more efficiently than deferoxamine. In rats with iron overload, very low concentrations of TLc-A lowered serum iron level after only three injections of the nanochelator, while deferoxamine was unable to reduce iron level after the same number of injections. Compared with deferoxamine, TLc-A significantly increased urinary iron excretion and reduced hepatic iron content. The toxicity study showed that the intraperitoneal median lethal dose for TLc-A was at least two times higher than that for deferoxamine. In conclusion, our in vitro and in vivo studies indicate that the novel nano chelator compound, TLc-A, offers superior performance in iron reduction than the commercially available and widely used deferoxamine.

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Urinary iron excretion in thalassaemia after desferrioxamine administration

Cited by 7 publications

References 15 publications

Long-term administration of desferrioxamine in thalassaemia major

Long-term administration of desferrioxamine in thalassaemia major

Drug Selection and Posology, Optimal Therapies and Risk/Benefit Assessment in Medicine: The Paradigm of Iron-Chelating Drugs

TLc-A, the leading nanochelating-based nanochelator, reduces iron overload in vitro and in vivo

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