Deferiprone (1,2-dimethyl-3-hydroxypyrid-4-one) alias L1, Kelfer, Ferriprox
Professor George J. Kontoghiorghes
Postgraduate Research Institute Science, Technology, Environment and Medicine
Ammochostou 3, CY 3021 Limassol, Cyprus. Tel: ++3575734615, e mail: pri_gjk@cylink.com.cy
Deferiprone 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 the body. Studies show that deferiprone is rapidly absorbed from the stomach. It appears in the blood minutes after the capsules are swallowed. In each patient, removal and excretion of iron depends on the dose and frequency of administration of the drug and the amount of iron overload. The major adverse effects, which have been observed in overall 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 yields valuable data that can contribute to the development of a diagnostic method for agranulocytosis, its prevention and general improvement of the therapy with Deferiprone.
The Journey across the years:
1981.Discovery, design, synthesis and physicochemical characterization.
1981-82. Iron binding, protein and cell studies in-vitro. Animal studies.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 the body. Studies show that deferiprone is rapidly absorbed from the stomach. It appears in the blood minutes after the capsules are swallowed. In each patient, removal and excretion of iron depends on the dose and frequency of administration of the drug and the amount of iron overload. The major adverse effects, which have been observed in overall 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 yields valuable data that can contribute to the development of a diagnostic method for agranulocytosis, its prevention and general improvement of the therapy with Deferiprone.
The Journey across the years:
1981.Discovery, design, synthesis and physicochemical characterization.
1982. Naming of L1 and other alpha - ketohydroxpyridines.
1983. Patented in the UK. Later patented in the USA, EEC and some other countries.
1982-86. Intensive chemical, biochemical, cell and animal studies.
1986. DHSS grants permission for clinical trials in UK.
1987. Simple, cheap synthesis of L1. First ever clinical trials in London.
1988. Multicenter 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 10 years.
1999. Registration of L1 in European, South American and Asian countries.
2000. 10th International Conference in Oral Chelators for the treatment of Thalassaemia and other Diseases. 22nd-26th March, 2000. Limassol , Cyprus.
For more information contact Professor George J. Kontoghiorghes at the above address.
Reproduced from : UKTS Website
PS: The above does not mention 1987 : 400 Thals in India put on the largest trial for L1 the in the world.
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