Abstract
The trimaltol iron complex (International Non-proprietary Name: ferric maltol) was originally designed, synthesised, and screened in vitro and in vivo in 1980–1981 by Kontoghiorghes G.J. following his discovery of the novel alpha-ketohydroxyheteroaromatic (KHP) class of iron chelators (1978–1981), which were intended for clinical use, including the treatment of iron deficiency anaemia (IDA). Iron deficiency anaemia is a global health problem affecting about one-third of the world’s population. Many (and different) ferrous and ferric iron complex formulations are widely available and sold worldwide over the counter for the treatment of IDA. Almost all such complexes suffer from instability in the acidic environment of the stomach and competition from other dietary molecules or drugs. Natural and synthetic lipophilic KHP chelators, including maltol, have been shown in in vitro and in vivo studies to form stable iron complexes, to transfer iron across cell membranes, and to increase iron absorption in animals. Trimaltol iron, sold as Feraccru or Accrufer, was recently approved for clinical use in IDA patients in many countries, including the USA and in EU countries, and was shown to be effective and safe, with a better therapeutic index in comparison to other iron formulations. Similar properties of increased iron absorption were also shown by lipophilic iron complexes of 8-hydroxyquinoline, tropolone, 2-hydroxy-4-methoxypyridine-1-oxide, and related analogues. The interactions of the KHP iron complexes with natural chelators, drugs, metal ions, proteins, and other molecules appear to affect the pharmacological and metabolic effects of both iron and the KHP chelators. A new era in the treatment of IDA and other possible clinical applications, such as theranostic and anticancer formulations and metal radiotracers in diagnostic medicine, are envisaged from the introduction of maltol, KHP, and similar lipophilic chelators.
Highlights
Normal biological, metabolic, physiological activities, and bodily functions are maintained in life due to the supply of essential nutrients, including transition metal ions, such as iron, copper, and zinc [1,2,3,4,5,6,7,8,9]
Trimaltol iron (International Non-proprietary Name: ferric maltol, Feraccru or Accrufer), and other lipophilic chelator iron complexes appear to offer improved therapeutic advantages in the treatment of iron deficiency anaemia (IDA) conditions in comparison to traditional oral iron formulations, which are generally linked to gastrointestinal toxic side effects, and in some cases, complications associated with exacerbation of other pre-existing underline diseases [11,23,34,36]
The findings suggested that the iron (59-Fe) absorbed following the oral administration of chelator iron complexes is diverted primarily to the bone marrow and utilised for the production of haemoglobin [144]
Summary
Metabolic, physiological activities, and bodily functions are maintained in life due to the supply of essential nutrients, including transition metal ions, such as iron, copper, and zinc [1,2,3,4,5,6,7,8,9]. Despite the wide availability of oral ferrous and ferric iron formulations, and of intravenous iron formulations in the treatment of IDA, there is scope for further improvement, especially in relation to safer and more effective targeting, with the ultimate aim to control increased iron absorption and delivery to haematopoietic and other tissues In this context, trimaltol iron (International Non-proprietary Name: ferric maltol, Feraccru or Accrufer), and other lipophilic chelator iron complexes appear to offer improved therapeutic advantages in the treatment of IDA conditions in comparison to traditional oral iron formulations, which are generally linked to gastrointestinal toxic side effects, and in some cases, complications associated with exacerbation of other pre-existing underline diseases [11,23,34,36]
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