Comparison between deferoxamine and deferiprone (L1) in iron‐loaded thalassemia patients

Taher, Ali T.; Sheikh-Taha, Marwan; Koussa, Suzanne; Inati, Adlette; Neeman, R.; Mourad, Fadi H.

doi:10.1034/j.1600-0609.2001.067001030.x

Cited by 57 publications

(42 citation statements)

References 23 publications

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“…Results of randomized clinical trials comparing DFO with DFP demonstrated no difference after 12 months of treatment in serum ferritin levels or liver iron concentration [23,24]. Similar results have been obtained in other studies [25,26,27]. …”

Section: Dfp Efficacysupporting

confidence: 76%

Deferiprone Chelation Therapy for Thalassemia Major

Galanello

Campus²

2009

Acta Haematol

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Iron overload is one of the major causes of morbidity in patients with thalassemia major. Deferiprone (DFP), an orally active iron chelator, emerged from an extensive search for new drugs to treat iron overload. Comparative studies have shown that at comparable doses the efficacy of DFP in removing body iron is similar to that of desferoxamine (DFO). In retrospective and prospective studies, DFP monotherapy was significantly more effective than DFO in the treatment of myocardial siderosis in thalassemia major. DFP can be used in combination with DFO in the management of severe iron overload. This chelation regimen is tolerable and attractive for patients unable to comply with standard DFO infusions or with inadequate response to DFP monotherapy. DFP has a well-known long-term safety profile. Agranulocytosis is the most serious side effect associated with its use, occurring in about 1% of the patients. More common but less serious side effects are gastrointestinal symptoms, arthralgia, zinc deficiency, and fluctuating transaminase levels.

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Section: Dfp Efficacysupporting

confidence: 76%

Deferiprone Chelation Therapy for Thalassemia Major

Galanello

Campus²

2009

Acta Haematol

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“…61 Patients receiving DFP, or DFP with DFO, showed a reduction in SF over time greater than patients who received DFO alone in two trials. 57,58 Three studies were analyzed for the comparison of DFX with DFO in severely iron loaded patients 9,11,43 ( Table 4). Altogether, 335 patients received DFX and 256 received DFO.…”

Section: Switching To An Alternative Iron Chelation Therapy In Patienmentioning

confidence: 99%

“…5,8 More cardiac events occurred while on DFO, and the analysis of cardiac disease free survival over the 5-year period was significantly more favorable in the DFP group. 8 LIC was measured at baseline and at the end of the trial in one study, 60 and SF in six, 8,[57][58][59][60][61] There was no significant difference in pre-and post-study LIC between patients using combined therapy and patients using DFO alone. 61 Patients receiving DFP, or DFP with DFO, showed a reduction in SF over time greater than patients who received DFO alone in two trials.…”

Section: Switching To An Alternative Iron Chelation Therapy In Patienmentioning

confidence: 99%

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Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders

Angelucci¹,

Barosi²,

Camaschella³

et al. 2008

Haematologica

182

156

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New measures of iron accumulation in liver and heart (superconducting quantum inference device and magnetic resonance imaging), and oral iron chelators (deferiprone and deferasirox) are available for managing iron overload in thalassemia major. To assure appropriate use of these new health technologies, the Italian Society of Hematology appointed a panel of experts to produce clinical practiceguidelines for the management of iron overload in thalassemia major and related disorders. The analytical hierarchy process, a technique for multicriteria decision analysis, was applied to relevant key questions in order to identify the alternative strategies, generate explicit criteria for their evaluation, and check how well the alternatives fulfilled the criteria. The result of a comprehensive systematic review of articles released from 1990 to 2007 was used as a source of scientific evidence to compare the decisional options pairwise, and select the final recommendation. Every step in the model was developed from questionnaires and group discussion. The resulting recommendations advise about which examination to carry out in order to plan iron chelation therapy, when to start iron chelation, which iron chelator to choose in regularly transfused patients, how to monitor iron chelation therapy, and when and how to switch standard therapy.

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“…As opposed to deferoxamine, which must be administered by subcutaneous infusion, the oral formulation of deferiprone simplifies treatment, improves patients' quality of life, and improves adherence (Tricta et al, 1996;Franchini and Veneri, 2004;Delea et al, 2007). Although the long-term safety profile of deferiprone is well defined, the mechanism of and factors involved in its adverse effects, such as gastrointestinal disturbances, arthralgia, neutropenia, and agranulocytosis, are unclear (Agarwal et al, 1990;Taher et al, 2001;Ceci et al, 2002;Cohen et al, 2003;Franchini and Veneri, 2004), thus emphasizing the need to decipher the underlying mechanisms and factors involved in these adverse effects. Deferiprone has good bioavailability, but its clearance is accelerated by rapid biotransformation: approximately 85% of the drug is metabolized to a nonchelating (inactive) 3-O-glucuronide conjugate (Huang et al, 2006) by UDP-glucuronosyltransferases (UGTs).…”

mentioning

confidence: 99%

Deferiprone Glucuronidation by Human Tissues and Recombinant UDP Glucuronosyltransferase 1A6: An in Vitro Investigation of Genetic and Splice Variants

Benoit‐Biancamano

Connelly²,

Villeneuve³

et al. 2008

Drug Metab Dispos

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ABSTRACT:Tissue iron overload constitutes a major health problem for people who require regular blood transfusions, such as those with ␤-thalassemia major. Deferiprone is a hydroxypyridinone iron chelator used therapeutically to remove this excess iron and prevent tissue damage. Deferiprone is metabolized by UDP-glucuronosyltransferases (UGTs) into deferiprone 3-O-glucuronide (DG), but a systematic evaluation of the contribution of individual human UGTs and the impact of genetic variations of UGTs have not been conducted. Sixteen human UGT1A and UGT2B were studied for deferiprone glucuronidation, and their clearances were compared in human tissue samples. DG was measured by liquid chromatography coupled with mass spectrometry. DG was primarily produced in vitro by UGT1A6, and a second glucuronide metabolite was discovered. UGT1A6, as well as liver and kidney human microsomes, had similar kinetic profiles and clearance (Cl int ‫؍‬ 1.4-3.0 l/min/mg), but clearance by intestinal microsomes was much lower (0.04 l/min/mg). Binding of deferiprone to microsomal preparations was not significant. Genetic variants of UGT1A6 had K m values similar to the reference protein (UGT1A6*1), but their V max values were reduced by 25 to 70%. The UGT1A6 splice variant isoform 2, detected in the liver and kidney, had no transferase activity for deferiprone. When UGT1A6_i2 was coexpressed with the classic UGT1A6_i1 isoform, velocity was reduced for deferiprone but remained similar for 4-nitrophenol or serotonin glucuronidation. In conclusion, deferiprone glucuronidation seems to depend almost totally on UGT1A6, especially in the liver. Genetic variations and differences in the expression of splice variants represent a potential source of variation in deferiprone metabolism.

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Comparison between deferoxamine and deferiprone (L1) in iron‐loaded thalassemia patients

Abstract: L1 had comparable efficacy as deferoxamine with minimal side effects and better compliance. Provided long term side effects are not encountered, L1 seems to be a valuable alternative iron chelator for patients unable or unwilling to use deferoxamine effectively.

Cited by 57 publications

References 23 publications

Deferiprone Chelation Therapy for Thalassemia Major

Deferiprone Chelation Therapy for Thalassemia Major

Italian Society of Hematology practice guidelines for the management of iron overload in thalassemia major and related disorders

Deferiprone Glucuronidation by Human Tissues and Recombinant UDP Glucuronosyltransferase 1A6: An in Vitro Investigation of Genetic and Splice Variants

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