Oral iron chelators – development and application

Chelation therapy for iron overload

“…Deferiprone (DFP) is an orally administered bidentate iron chelator (1,2 dimethyl-3-hydroxypyrid-4-one [mw = 139 d]; L1, CP20; Kelfer, Cipla Ltd., Mumbai, India; Ferriprox, Apotex, Toronto ON, Canada) or treatment of iron overload in patients with -thalassemia major in whom DFO is contraindicated or inadequate (Table 2) [3]. DFP therapy has been reviewed extensively.…”

“…A significant decline in mean hepatic iron concentrations occurred infrequently in patients with transfusion-dependent anemia whose iron overload was treated with DFP [15]; no reports exist of deferasirox therapy in patients with hepatic functional impairment. DFP and deferasirox cause elevated serum aminotransferase concentrations [3,5,28]. Altogether, clinical trials must be designed to determine if oral chelation therapy can eliminate hepatic iron deposits without causing additional liver injury and if hepatic fibrosis and cirrhosis caused by iron overload can be reversed.…”

Role of deferiprone in chelation therapy for transfusional iron overload

“…20 A letter in response to these findings noted that when the same biopsy specimens were reviewed by another hepatopathologist in a masked manner but excluding specimens with insufficient numbers of portal tracts, no progression of liver fibrosis was found in the patients treated with deferiprone. 68 The description of increased rates of iron accumulation and hepatotoxicity in iron-loaded gerbils after treatment with dimethyl-3-hydroxypyrid-4-1 (CP94), 69 a compound closely related to deferiprone, 70,71 has been identified as evidence supportive of the hepatotoxicity and fibrogenic effect of deferiprone. 20,26 However, CP94 (dimethyl-3-hydroxypyrid-4-1) and deferiprone (dimethyl-3-hydroxypyrid-4-1) are different in their biologic activity.…”

Combined chelation of bi-functional bis-hydroxypiridinone and mono-hydroxypiridinone: Synthesis, solution and in vivo evaluation

“…Due to drawbacks associated with DFO, other iron-chelating drugs have been discovered, including 1,2-dimethyl-3-hydroxy-4-pyridinone (commercially available as deferriprone, DFP), an orally active iron-chelating drug also currently used in b-thalassemic patients [4,5]. The combined chelation therapy with DFO and DFP is also being used in special situations of regularly transfused iron-overload patients [6][7][8][9], improving the metal mobilization, either in an additive or a synergistic manner, probably through iron ''shuttling" from DFP to DFO [10].…”