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Deferiprone
 
The deferiprone-iron complex; 3 (L1) : iron stoichiometry
 
  Deferiprone is a bidentate molecule and forms a 3:1 octahedral complex with iron, which is excreted almost exclusively via the kidneys.

Deferiprone is used in the removal of excess iron from the body, but may also be used in the detoxification of other metals such as aluminium in haemodialysis patients, plutonium used in the nuclear industry, and uranium used by the military.

 
 
Deferiprone

Deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one or L1) is the first oral iron chelator used clinically, mainly in thalassaemia patients, where the annual birth rate worldwide is estimated to be 100000. Deferiprone belongs to the family of the alpha-ketohydroxpyridines, a relatively new class of chelating agents, some of which are naturally occurring. These have high affinity for binding iron and are able to remove it from proteins that are transporting and storing it in the body, largely sparing other biologically important metals. These chelators are stable in conditions that exist in the human digestive system and are readily absorbed. Deferiprone has undergone extensive trials in hundreds of patients all over the world and has proved to be orally effective in removing excess iron from various parts of the body of iron-loaded patients, including the liver and particularly the heart. 

Studies show that Deferiprone is rapidly absorbed from the stomach and appears in the blood minutes after ingestion. Removal and excretion of iron depends on the dose and frequency of administration of the drug and the amount of iron overload in the patient. 

The major adverse effects, which have been observed in about 10% of the patients during worldwide clinical trials over a period of ten years, have been transient musculoskeletal
and joint pains, neutropenia and agranulocytosis, gastric intolerance and zinc deficiency. Of these, perhaps the most disturbing is agranulocytosis, affecting less than 0.6% of the patients. In patients with agranulocytosis a substantial reduction or total absence of a group of white cells called granulocytes is observed, which amounts to rendering the body's immune system fatally weak. This is the reason the focus of the mandatory monitoring procedure is primarily on levels of white blood cells and platelets. The monitoring not only helps to safeguard the well being of the patient but also yields valuable data that can contribute to the development of a diagnostic method for agranulocytosis and improvement of the therapy with Deferiprone.

The journey across the years 

1981

Discovery, design, synthesis and physicochemical characterisation of L1. 

1981-1982

Iron binding, protein and cell studies in-vitro. Animal studies. 

1982

Naming of L1 and other alpha-ketohydroxpyridines.

1983

Patented in the UK. Later patented in the USA, EEC and various other countries.

1982-1986

Intensive chemical, biochemical, cell and animal studies. 

1986

The UK Department of Health grants permission for clinical trials in the UK.

1987

Simple, cheap synthesis of L1. First-ever clinical trials in London, UK.

1988

Multicentre clinical trials begin worldwide.

1989

First publications on joint/musculoskeletal toxicity and agranulocytosis (London).

1990

Pharmacokinetic and metabolic properties characterisation of L1 in patients.

1992

Approved BAN and INN name for L1: Deferiprone.

1994

Registration of L1 in India, where now more patients are using L1 than Desferal.

1995

Clinical use and multicentre clinical studies continue.

1998

Over 5000 patients in 35 countries have been using L1, some daily for over 12 years.

1999

Registration of L1 in European, South American and Asian countries.

2000

The new, simple, one-step synthesis of L1 is patented in Greece.

2002

Worldwide use of L1 following recent findings regarding depletion of iron from the heart (which is the main cause of death in thalassaemic patients).

 

 
 

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