Disease relevance of deferiprone

• 1,2-Dimethyl-3-hydroxypyrid-4-one, an orally active chelator for treatment of iron overload [1].
• Efficacy and possible adverse effects of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in thalassemia major [2].
• Eleven patients with beta thalassemia major were entered into the trial of the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) [2].
• The effect of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) on liver nonheme iron, lipid peroxidation and hepatic fat accumulation in the intragastric feeding rat model for alcoholic liver disease was studied [3].
• In an attempt to reduce the toxicity of the 3-hydroxypyrid-4-ones, the more hydrophilic derivatives of kojic acid were explored and compared to the standard, 1,2-dimethyl-3-hydroxypyrid-4-one, L1 [4].

High impact information on deferiprone

• A comparative study of the iron-clearing properties of subcutaneously (SC) administered deferoxamine (DFO) with those of orally administered 1,2-dimethyl-3-hydroxypyrid-4-one (CP20) and 1,2-diethyl-3-hydroxypyrid-4-one (CP94) is presented [5].
• Recently, the focus has turned to drugs that have been used successfully in the treatment of a variety of other diseases, for example the iron chelating drug deferiprone or 1,2-dimethyl-3-hydroxypyrid-4-one (L1), which is used in thalassaemia and ethane-1-hydroxy-1,1-bisphosphonate (EHBP), which is used in osteoporosis [6].
• Deferiprone (L1 or 1,2-dimethyl-3-hydroxypyrid-4-one) is the world's first and only orally active iron chelating drug, which is effective and inexpensive to synthesise thus increasing the prospects of making it available to most thalassaemia patients in third world countries who are not currently receiving any form of chelation therapy [7].
• Relationship between the pharmacokinetics and iron excretion pharmacodynamics of the new oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one in patients with thalassemia [8].
• In cultured Kupffer cells isolated from normal rats, treatment with a lipophilic iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one (L1), markedly reduced lipopolysaccharide (LPS)-induced NF-kappaB activation and expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 [9].

Chemical compound and disease context of deferiprone

• The oral efficacy of the oral iron chelators 1,2-dimethyl-3-hydroxypyrid-4-one (CP20), 1,2-diethyl-3-hydroxypyrid-4-one (CP94) and desferrioxamine B (DFO) has been compared with intraperitoneal DFO in an experimental model of iron overload with similar biochemical and biophysical characteristics to those observed for human genetic haemochromatosis [10].
• BACKGROUND: Deferiprone [(1,2-dimethyl-3-hydroxypyrid-4-one) (L1)], is the first orally active iron chelating agent to reach clinical trials in patients with chronic iron overload [11].

Biological context of deferiprone

• Single-dose and steady-state pharmacokinetics of the new oral iron chelator, 1,2-dimethyl-3-hydroxypyrid-4-one (L1) were studied in 14 patients with thalassemia and correlated with iron excretion [8].

Anatomical context of deferiprone

• Specific labelling of a chelatable "cold" iron pool in hepatocytes by 59Fe derived from ferritin showed this pool to be equally accessible to parenteral doses of both chelators and also to oral 1,2-dimethyl-3-hydroxypyrid-4-one, which is an effective oral iron chelating agent that removes iron from parenchymal cells [12].

Associations of deferiprone with other chemical compounds

• The pursuit of orally available Fe(III) chelating agents has resulted in several clinical trials of 1,2-dimethyl-3-hydroxypyrid-4-one (CP20) [13].
• Studies of aluminium mobilization in renal dialysis patients using the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one [14].

Gene context of deferiprone

• Ten RA patients with ACD were treated with the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) [15].
• Impaired erythropoietin responsiveness to the anaemia in rheumatoid arthritis. A possible inverse relationship with iron stores and effects of the oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one [15].
• Treatment of the BDL animals with 1,2-dimethyl-3-hydroxypyrid-4-one (L-1), a lipophilic iron chelator, suppressed the increases in hepatic TBARS by 64%, plasma alanine aminotransferase by 45%, and HM TNF-alpha and IL-6 mRNA by > 84% [16].
• Deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one, L1, CAS 30652-11-0) is a new chelating drug used worldwide for the treatment of iron overloading conditions [17].

Analytical, diagnostic and therapeutic context of deferiprone

• OBJECTIVE: To examine the effect of frequency of oral administration of 1,2-dimethyl-3-hydroxypyrid-4-one (L1) on urinary iron excretion [18].
• We have been evaluating the orally active iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in both preclinical and clinical trials [19].
• The enhanced rate of NTBI uptake in Fe-loaded cells reverted to control rates after treatment with therapeutic concentrations of Fe chelators deferoxamine, 1,2-dimethyl-3-hydroxypyrid-4-one and 1,2-diethyl-3-hydroxypyrid-4-one under conditions where approximately 80% of the cellular Fe was removed by chelation [20].
• 1,2-Dimethyl-3-hydroxypyrid-4-one caused a decrease in iron absorption at a high dose (10 mg) by comparison to the control group but it did not significantly alter iron absorption at a lower dose (2 mg) [21].

References