Deferiprone

Absorption

Deferiprone is absorbed in the upper gastrointestinal tract. Absorption is rapid with maximum plasma concentrations occurring after 1 hour in the fasted state and after 2 hours in the fed state.

Toxicity

Agranulocytosis and neutropenia may occur, which can lead to fatal infections. Hepatoxicity is also possible. Most common side effects that lead to discontinuation of therapy were the gastrointestinal adverse effects (diarrhea, ulcer, nausea, gastrointestinal disturbances)

Description

Deferiprone, the first oral iron chelator, was marketed in India for the management of thalassaemia. Patients with thalassaemia, a blood related genetic disorder, require life time transfusion which causes excessive deposition of iron in liver and spleen, subsequent damage to organs and eventually death unless iron is removed by a chelator. Deferiprone is a potent iron chelator that mobilizes excessive iron from iron storage proteins ferritin and hemosiderin, from iron saturated transferrin and lactoferrin, but not from hemoglobin. The deferiprone-iron complex is excreted in urine and bile. Deferiprone was reportedly well accepted by patients and no hematological toxicity was observed. Deferiprone has also been demonstrated as an effective and safe chelator in the mobilization of aluminum.

Chemical properties

White Needles

Originator

Cipla (India)

The Uses of Deferiprone

A chelator that could replace disferrioxamine. It is orally and parenterally effective in the removal of iron in vivo from rabbits and mice and also from transferrin and ferritin in vitro

The Uses of Deferiprone

3-Hydroxy-1,2-dimethyl-4(1H)-pyridone (OH-pyridone) may be used in the bacterial killing assays. It has been employed as hydroxyketone chelating agent and its cytotoxic action against oral human normal and tumor cell lines has been evaluated.

What are the applications of Application

Deferiprone is a chelator that removes transferrin and ferritin in vitro

Background

Deferiprone is an oral iron chelator used as a second line agent in thalassemia syndromes when iron overload from blood transfusions occurs. Thalassemias are a type of hereditary anaemia due a defect in the production of hemoglobin. As a result, erythropoiesis, the production of new red blood cells, is impaired. FDA approved on October 14, 2011.

Indications

Deferiprone is indicated in thalassemia syndromes when first line chelation agents are not adequate to treat transfusional iron overload.

Definition

ChEBI: Deferiprone is a member of the class of 4-pyridones that is pyridin-4(1H)-one substituted at positions 1 and 2 by methyl groups and at position 3 by a hydroxy group. A lipid-soluble iron-chelator used for treatment of thalassaemia. It has a role as an iron chelator and a protective agent.

brand name

Kelfer

General Description

3-Hydroxy-1,2-dimethyl-4(1H)-pyridone (Hdpp, Deferiprone) is a hydroxy ketone derivative. It reacts with uranyl salts [UO₂(NO₃)₂] in aqueous acidic solution to afford mono nuclear complexes ([UO₂(dpp)(Hdpp)₂(H₂O)]ClO₄). X-ray studies have been conducted to examine the structure and geometry of these complexes.

Clinical Use

Orally administered chelator:
Treatment of transfusional iron overload

Metabolism

Deferiprone is mainly metabolized by UGT1A6 to the 3-O-glucuronide metabolite. This metabolite cannot chelate iron.

Metabolism

Deferiprone is hepatically metabolised to an inactive glucuronide metabolite and is excreted mainly in the urine as the metabolite and the iron-deferiprone complex, with a small amount of unchanged drug.

References

1) Hider and Hoffbrand (2018),?The Role of Deferiprone in Iron Chelation; N. Engl. J. Med.,?379?2140 2) Sripetchwandee?et al.?(2016),?A combination of an iron chelator with an antioxidant effectively diminishes the dendritic loss, tau-hyperphosphorylation, amyloid-β accumulation and brain mitochondrial dynamic disruption in rats with chronic iron-overload., Neuroscience?332?191 3) Liu?et al.?(2018),?Iron and Alzheimer’s Disease: From Pathogenesis to Therapeutic Implications;?Front. Neurosci,?12?632