Dietary supplementation of baicalin and quercetin attenuates iron overload induced mouse liver injury

The introduction of new iron chelating drugs may ultimately improve iron-chelation therapy for patients with iron overload diseases such as thalassaemia and other disorders. In this paper, the in vivo effects of baicalin and quercetin on iron overload induced liver injury were studied on mice. It was found that when iron-dextran induced iron overload mice were fed baicalin or quercetin containing diet (1% w/w) for 45 days, both flavonoids significantly inhibited iron overload induced lipid peroxidation and protein oxidation of liver, decreased hepatic iron and hepatic collagen content, increased the serum non-heme iron level but not serum ferritin level. Flavonoids supplementation also increased the excretion of iron through feces. In vitro study demonstrated that both flavonoids could release iron from ferritin. These results indicate that besides acting as antioxidants, both flavonoids can also release iron from liver and finally excrete it through feces. The present study provides further support for flavonoids to be medicines for iron overload diseases.     

Comparison of oxidative stress markers after intravenous administration of iron dextran, sodium ferric gluconate, and iron sucrose in patients undergoing hemodialysis

STUDY OBJECTIVE: To compare non-transferrin-bound iron and markers of oxidative stress after single intravenous doses of iron dextran, sodium ferric gluconate, and iron sucrose. DESIGN: Prospective, open-label, crossover study. SETTING: University-affiliated general clinical research center. PATIENTS: Twelve ambulatory patients undergoing hemodialysis. INTERVENTION: Patients received 100 mg of intravenous iron dextran, sodium ferric gluconate, and iron sucrose in random sequence, with a 2-week washout period between treatments. MEASUREMENTS AND MAIN RESULTS: Serum samples for transferrin saturation, non-transferrin-bound iron, and malondialdehyde (MDA; marker of lipid peroxidation) were obtained before (baseline) and 30, 60, 120, and 360 minutes and 2 weeks after each iron infusion. A serum sample for hemeoxygenase-1 (HO-1) RNA was obtained at baseline and 360 minutes after infusion. Non-transferrin-bound iron values were significantly higher 30 minutes after administration of sodium ferric gluconate and iron sucrose compared with iron dextran (mean +/- SEM 10.1 +/- 2.2, 3.8 +/- 0.8, and 0.23 +/-0.1 microM, respectively, p<0.001 for sodium ferric gluconate vs iron dextran, p = 0.002 for iron sucrose vs iron dextran). A significant positive correlation was noted between transferrin saturation and the presence of non-transferrin-bound iron for sodium ferric gluconate and iron sucrose (r2 = 0.37 and 0.45, respectively, p<0.001) but not for iron dextran (r2 = 0.09). After sodium ferric gluconate, significantly more samples showed increases in MDA levels from baseline compared with iron sucrose and iron dextran (p = 0.006); these increased levels were associated with the presence of non-transferrin-bound iron, baseline transferrin saturation above 30%, baseline transferrin levels below 180 mg/dl, and ferritin levels above 500 ng/ml (p<0.05). However, only a transferrin level below 180 mg/dl was independently associated (odds ratio 4.8, 95% confidence interval 1.2-15.3). CONCLUSION: Iron sucrose and sodium ferric gluconate were associated with greater non-transferrin-bound iron appearance compared with iron dextran. However, only sodium ferric gluconate showed significant increases in lipid peroxidation. The relationship between non-transferrin-bound iron from intravenous iron and oxidative stress warrants further exploration.     

Bioavailability of trivalent iron in oral iron preparations. Therapeutic efficacy and iron absorption from simple ferric compounds and high- or low-molecular weight ferric hydroxide-carbohydrate complexes.

All available results from critical hemoglobin regeneration tests, postabsorption serum iron concentration studies, 59Fe erythrocyte incorporation and 59Fe whole-body retention measurements demonstrate that humans do absorb ferrous iron between 4 and 10 times (in the average about 5 times) better than ferric iron from therapeutic oral 50--250 mg iron doses. Ferrous sulfate iron is 3 to 4 times better available than the iron from ferric ammonium citrate or sulfate. Whereas 100 mg of ferrous sulfate iron/day are sufficient for an optimal oral compensation iron therapy and to produce initial hemoglobin regeneration rates of about 0.26 g/100 ml/day, 400 to 1000 mg of ferric iron/day are necessary for the same therapeutic effect because of the poor bioavailability of ferric iron. The ratio of the dose-absorption relationships for ferric and ferrous 59Fe was shown to decrease from 0.43 for a diagnostic 0.56 mg Fe dose to 0.21 for the therapeutic 50 mg Fe dose in subjects with normal iron stores. Absorption ratios of 0.65 for the 0.56 mg Fe dose and 0.26 for the 50 mg Fe dose were measured in subjects with depleted iron stores. At all dose levels the superior bioavailability of ferrous iron was demonstrable. A high-molecular weight ferric hydroxide-carbohydrate complex (MW similar to 30 000) was palatable but so poorly absorbed that is was practically without effect on hemoglobin regeneration even at a daily 300 mg Fe dose. Following several warnings such a useless commerecial oral iron preparation was finally withdrawn from the market. The iron from any high-molecular weight carbohydrate complex of ferric hydroxide has to be suspected to be poorly absorbed and therefore therapeutical useless, unless the opposite has been demonstrated with a reliable bioassay (59Fe absorption whole-body retention and hemoglobin regeneration test). A low-molecular weight so-called ferric hydroxide-fructose complex was shown to contain iron of more or less the same poor bioavailability as contained in ferric chloride since the iron from ferrous sulfate was about 5 times better absorable. The good absorption of ferrous sulfate iron was not further augmented by even very large oral doses of fructose since this carbohydrate did not improve the ferrous iron absorption at a fructose: Fe molar ratio of 106:1. Trivalent iron in simple compounds like ferric ammonium citrate or in low- and high-molecular weight carbohydrate complexes of ferric hydroxide is so poorly available for intestinal iron absorption in man that it cannot be used for a fast and reliable oral iron therapy with reasonably low doses as it can be easily practised with quick-lease preparations of ferrous sulfate at a 100 mg Fe2     

Disposition, accumulation and toxicity of iron fed as iron (II) sulfate or as sodium iron EDTA in rats.

A study was performed to provide data on the disposition, accumulation and toxicity of sodium iron EDTA in comparison with iron (II) sulfate in rats on administration via the diet for 31 and 61 days. Clinical signs, body weights, food consumption, food conversion efficiency, hematology, clinical chemistry and pathology of selected organs were used as criteria for disclosing possible harmful effects. Determination of iron and total iron binding capacity in blood plasma and non-heme iron analysis in liver, spleen and kidneys were used to assess the disposition and accumulation of iron originating from sodium iron EDTA or iron (II) sulfate. It was concluded that, under the conditions of the present study, iron is accumulated from the diet in liver, spleen and kidneys in a dose-dependent manner, and iron derived from FeEDTA is taken up and/or accumulated less efficiently in liver and spleen than iron from FeSO(4). Moreover, feeding iron up to 11.5 and 11.2 mg/kg body weight/day, derived from FeSO(4) and FeEDTA, respectively, did not result in tissue iron excess nor in any other toxicologically significant effects.     

静脉注射右旋糖酐铁优于口服琥珀酸亚铁治疗血液透析铁缺乏贫血

目的 :比较静脉铁剂与口服铁剂在治疗透析相关性贫血中的疗效。方法 :2 3例病人随机分入静脉铁剂组 (静脉组 )和口服铁剂组 (口服组 ) ,前者给予右旋糖酐铁 10 0mg ,在病人每次透析中经透析器的静脉端输入 ,直至完成总预计补铁量 (15 36±s2 5 4 )mg ,观察时间约 6～ 8wk ;后者给予琥珀酸亚铁 2 0 0mg ,po ,每日 3次 ,连续服用 8wk。 2组病人均同时使用促红细胞生成素治疗。结果 :静脉铁剂组治疗 8wk后 ,血红蛋白增长 (15± 12 )g·L- 1,红细胞比容增长 (4± 3) % ,血清铁蛋白增长 (330±15 8) μg·L- 1,而口服铁剂组三者分别为 (3± 11)g·L- 1,(0 .7± 2 .3) %和 (10 2± 2 2 4 ) μg·L- 1,差异有显著意义 (P <0 .0 5 ) ;静脉铁剂组的有效率为 5 5 % ,而口服铁剂组为 2 5 % ,两者差异有非常显著意义 (P<0 .0 1)。不良反应发生率静脉铁剂组是 9% ,口服铁剂组为 33%。结论 :静脉铁剂在治疗血液透析贫血病人铁缺乏时安全有效 ,并优于口服铁剂     

Current and future therapy in haemochromatosis and Wilson's disease

There have been several new developments in the treatment of iron and copper overload disorders, such as haemochromatosis, thalassaemia and Wilson's disease. Clinical trials of orally administered iron chelators, both as monotherapy and in combination with deferoxamine, are in progress around the world. Several new chelators are now being introduced in clinical trials. Future therapies for iron overload may comprise of oral iron binding agents capable of preventing dietary iron absorption from the diet. The characterisation of specific iron transporters such as the divalent metallic transporter and ferroportin may hold promise for the development of 'smart' compounds capable of blocking iron transport. Several new agents are now available for the management of Wilson's disease, including trientine, zinc and tetrathiomolybdate. This review, will discuss the pathogenesis, and current and future therapies for iron and copper overload disorders.     

Fatal anaphylactic reaction to iron sucrose in pregnancy

Iron-deficiency anemia in pregnancy can have serious deleterious effects for both mother and fetus. Parenteral iron therapy in iron-deficiency anemia is recommended in patients where oral iron therapy is ineffective due to malabsorption states and non-compliance. Compared to oral iron therapy, intravenous iron results in much more rapid resolution of iron-deficiency anemia with minimal adverse reactions. Iron sucrose has a favorable safety profile and is an alternative to other forms of parenteral iron therapy in correction of iron stores depletion. Immune mechanisms and iron agent releasing bioactive, partially unbound iron into the circulation, resulting in oxidative stress appears to cause severe adverse reactions. Although iron sucrose has a favorable safety profile in comparison to other parenteral iron preparations, this report highlights a fatal anaphylactic shock to iron sucrose in a pregnant woman with severe iron deficiency non-compliant to oral iron therapy.KEY WORDS: Anaphylactic Reaction, fatal, iron sucrose, pregnancy     

北京天坛医院铁制剂利用5年动态研究

统计北京天坛医院１９９４年１月至１９９８年６月铁制剂的购药数量,金额,采用ＷＨＯ推荐的“限定日剂量（ＤＤＤ）”作为药物研究的剂量单位,计算用药频率及日均费用。结果显示,我院铁制剂利用以口服铁剂为主,其中部分为进口铁剂;口服铁剂中,多糖铁复合物胶囊、枸橼酸铁铵片应用较多,琥珀酸亚铁片作为预防和治疗缺铁性贫血的首选药物;注射铁剂中,右旋糖酐铁注射液应用较多。     

Current and future therapy in haemochromatosis and Wilson’s disease

There have been several new developments in the treatment of iron and copper overload disorders, such as haemochromatosis, thalassaemia and Wilson’s disease. Clinical trials of orally administered iron chelators, both as monotherapy and in combination with deferoxamine, are in progress around the world. Several new chelators are now being introduced in clinical trials. Future therapies for iron overload may comprise of oral iron binding agents capable of preventing dietary iron absorption from the diet. The characterisation of specific iron transporters such as the divalent metallic transporter and ferroportin may hold promise for the development of ‘smart’ compounds capable of blocking iron transport. Several new agents are now available for the management of Wilson’s disease, including trientine, zinc and tetrathiomolybdate. This review, will discuss the pathogenesis, and current and future therapies for iron and copper overload disorders.     

A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer®), a new intravenous iron preparation and its clinical implications

The treatment of iron deficiency anemia with polynuclear iron formulations is an established therapy in patients with chronic kidney disease but also in other disease areas like gastroenterology, cardiology, oncology, pre/post operatively and obstetrics’ and gynecology. Parenteral iron formulations represent colloidal systems in the lower nanometer size range which have traditionally been shown to consist of an iron core surrounded by a carbohydrate shell. In this publication, we for the first time describe the novel matrix structure of iron isomaltoside 1000 which differs from the traditional picture of an iron core surrounded by a carbohydrate. Despite some structural similarities between the different iron formulations, the products differ significantly in their physicochemical properties such as particle size, zeta potential, free and labile iron content, and release of iron in serum. This study compares the physiochemical properties of iron isomaltoside 1000 (Monofer®) with the currently available intravenous iron preparations and relates them to their biopharmaceutical properties and their approved clinical applications. The investigated products encompass low molecular weight iron dextran (CosmoFer®), sodium ferric gluconate (Ferrlecit®), iron sucrose (Venofer®), iron carboxymaltose (Ferinject®/Injectafer®), and ferumoxytol (Feraheme®) which are compared to iron isomaltoside 1000 (Monofer®). It is shown that significant and clinically relevant differences exist between sodium ferric gluconate and iron sucrose as labile iron formulations and iron dextran, iron carboxymaltose, ferumoxytol, and iron isomaltoside 1000 as stable polynuclear formulations. The differences exist in terms of their immunogenic potential, safety, and convenience of use, the latter being expressed by the opportunity for high single-dose administration and short infusion times. Monofer is a new parenteral iron product with a very low immunogenic potential and a very low content of labile and free iron. This enables Monofer, as the only IV iron formulation, to be administered as a rapid high dose infusion in doses exceeding 1000 mg without the application of a test dose. This offers considerable dose flexibility, including the possibility of providing full iron repletion in a single infusion (one-dose iron repletion).     

Molecular factors and mechanisms affecting iron and other metal excretion or absorption in health and disease: the role of natural and synthetic chelators

The maintenance of iron and other essential metal ion balance in humans is based on the presence of homeostatic mechanisms of regulatory absorption, storage, re-utilisation and excretion. There are a number of factors and mechanisms that can affect the level of iron excretion or absorption and overall body iron stores. Net iron loss due to increased iron excretion by comparison to dietary iron absorption is considered as one of the causes of iron deficiency anaemia. Body iron loss greater than normal has been shown in many other conditions. These include the increase in urinary iron excretion observed in iron loaded patients, the substantial reduction in serum ferritin and liver iron of ex-thalassaemia patients several years following bone marrow transplantation and the increase in iron excretion in normal individuals following long term sport activities. There are differences in the metabolism, mode of action, interactions with the iron pools and routes of iron excretion, of the iron chelating drugs deferiprone (L1), deferoxamine and other experimental chelators such as ICL670 in iron-loaded patients. Naturally occurring chelators and some synthetic drugs are known to bind iron and affect iron absorption and excretion. The molecular characteristics of naturally occurring or synthetic chelators can influence other aspects of iron metabolism in addition to iron absorption or excretion. Similar mechanisms and factors can affect the metabolism of other essential metals. The understanding of the mechanisms involved in iron excretion and their overall effects on body iron levels can facilitate the design of new chelators and improved therapeutic protocols for the treatment of conditions of iron and other metal metabolic imbalance and toxicity.     

Monitoring intracellular labile iron pools: A novel fluorescent iron(III) sensor as a potential non-invasive diagnosis tool

The physiological and pathophysiological importance of intracellular redox active "labile" iron has created a significant need for improved noninvasive diagnostic tools to reliably monitor iron metabolism in living cells. In this context, fluorescent iron-sensitive chemosensors in combination with digital fluorescence spectroscopic methods have proven to be highly sensitive and indispensable tools to determine cellular iron homeostasis. Recently, application of fluorescent iron sensors has led to the identification of a complex sub-cellular iron compartmentation. Cell organelle-specific iron sensors will significantly contribute to enhance fundamental knowledge of cellular iron trafficking, representing a crucial prerequisite for the future development of therapeutic strategies in iron dysregulatory diseases. Here we present physicochemical characterization and functional investigation of a new 3-hydroxypyridin-4-one based fluorescent iron(III) sensor, exclusively monitoring labile iron pools in the endosomal/lysosomal compartments. In vitro studies of the fluorescein labeled probe were carried out in murine bone marrow derived macrophages. Endosomal/lysosomal accumulation of the probe was revealed by confocal microscopy. Flow cytometry analyses demonstrated high sensitivity of the probe towards exogenous alterations of intracellular iron concentrations as well as in response to the chelation potency of iron chelators, clinically approved for treatment of iron-overload related diseases.     

Intraperitoneal N-acetylcysteine for acute iron intoxication in rats

Free radical formation and release of oxidant agents have been suggested as possible mechanisms for tissue damage in acute iron intoxication. N-acetylcysteine (NAC), a glutathione substitute and an antioxidant, is widely used as an antidote for various intoxications. Our aim was to determine whether intraperitoneal (i.p.) NAC would reduce the mortality of rats after acute, toxic oral doses of iron. Male Wistar rats were studied in three phases. In the first phase, animals were assigned to groups 1 (distilled water by gavage) and 2 (i.p. NAC) and observed for survival. In the second phase, rats were assigned to groups 3 (400?mg/kg elemental iron orally) and 4 (400?mg/kg elemental iron, followed by 150?mg/kg i.p. NAC). Survival was observed. Because most rats in Group 3 died within 90 minutes after iron administration, a third phase was conducted in order to allow for comparison of iron and transaminase serum levels after the administration of iron and NAC (group 5: n?=?10). Mortality was significantly lower in rats treated with iron and NAC, compared to those treated with iron (P?=?0.016). Median serum iron level was significantly lower among rats treated with iron and NAC, compared with rats treated with iron alone (P?=?0.002). In a rat model of acute iron intoxication, i.p. administration of NAC may decrease serum iron levels and mortality.     

Optimal management strategies for chronic iron overload

Iron overload is characterised by excessive iron deposition and consequent injury and dysfunction of target organs, especially the heart, liver, anterior pituitary, pancreas and joints. Iron overload disorders are common worldwide and occur in most major race/ethnicity groups. Physiological mechanisms to excrete iron are very limited. Thus, all patients with iron overload need safe and effective treatment that is compatible with their co-existing medical conditions. Treatments for iron overload include phlebotomy and erythrocytapheresis that remove iron predominantly as haemoglobin, and chelation therapy with drugs that bind excess iron selectively and increase its excretion. The most important potential benefits of therapy are preventing deaths due to cardiac siderosis and hepatic cirrhosis. Preventing iron-related injury to endocrine organs is critical in children. Successful treatment or prevention of iron overload increases quality of life and survival in many patients. This article characterises the major categories of iron overload disorders, tabulates methods to evaluate and treat iron overload, and describes treatment options for iron overload disorders. Research needed to advance knowledge about treatment of iron overload is proposed.     

Clinical pharmacokinetics of iron preparations

The principle of iron conservation is the basis of iron metabolism; the normal basal loss of iron from the body is about 1 mg daily in a 70 kg man and 0.8 mg in a 55 kg woman. Iron is lost mainly by the menstrual and gastrointestinal routes. The total iron requirement during pregnancy is 800 mg; in the last month the requirement may amount to 7 to 8 mg/day. Supplementary iron is recommended for many menstruating women, and during the latter part of pregnancy. Correct fetal iron metabolism is ensured by proper maternal iron status, although there are contradictory opinions and findings about the relationship between maternal and fetal iron metabolism. Preterm infants fed on breast milk have a negative iron balance, and require an iron intake of about 0.6 mg/kg/day, and 3.4 mg/1 g haemoglobin, to compensate for intestinal and venesection iron losses, respectively. The absorption of supplementary iron by the preterm infant is a linear function of intake. Preterm infants do not require iron supplements when given repeated blood transfusions. During lactation the total iron losses of the mother are 1 mg/day, and thus no supplementary iron is needed if the iron metabolism has been in balance during the pregnancy. Serum ferritin concentration decreases continuously when iron stores in the body are reduced, and totally empty iron stores are the only known reasons for low serum ferritin concentration. Despite depleted iron stores, serum ferritin concentration can be normal or higher than normal in protein-energy malnutrition, up to 3 months after major surgery, in acute liver damage, in some patients with prolonged hyperglycaemia due to diabetes mellitus, in acute lobar pneumonia, active pulmonary tuberculosis and rheumatoid arthritis on gold therapy, in sepsis secondary to marrow hypoplasia induced by chemotherapy, in heavy drinkers and for a few days after myocardial infarction. In haemochromatosis, iron is deposited in liver (producing fibrosis), pancreas, endocrine glands and heart. The rise in the level of iron in the body is due to increased absorption and/or increased intake. This pathology may occur in transfusions, in alcoholism (especially when alcoholic beverages are contaminated with iron and the diet is low-protein), in several liver diseases, in congenital transferrin deficiency and in idiopathic disease. Patients susceptible to haemochromatosis should receive a low-iron diet. Serum ferritin determination may be helpful in early identification of susceptible members of a family with idiopathic familial haemochromatosis, but transferrin saturation is not a good indicator of either iron depletion or iron overload.(ABSTRACT TRUNCATED AT 400 WORDS)     

Determination of iron limiting values according to PH. EUR. using 1,3-dibromo-5,5-dimethylhydantoin (DBH) instead of elemental bromine. Analytical methods of pharmacopoeias with DBH in respect to environmental and economical concern. Part 8

PH. EUR. 2002 uses elemental bromine performing iron limit tests for maleic acid (iron 5 ppm) and titanium dioxide (iron 200 ppm). 1,3-Dibromo-5,5-dimethylhydantoin (DBH) can replace bromine water. For the iron limit test of maleic acid bivalent iron is oxidized to trivalent iron by bromine resp. DBH, because the unsaturated, in high concentration existing acid reacts substantially slower. On the other hand maleic acid removes the excess of bromine. The bromine oxidation for the iron limiting values of titanium dioxide according to the pharmacopoeia is not required. Metallic iron as well as ferrous salts are converted to trivalent iron, when the titanium test solution is prepared by boiling with concentrated sulphuric acid in the presence of anhydrous sodium sulphate.     

Influence of inorganic and organic iron compounds on parameters of cell growth and survival in human colon cells

Increased risk for development of colon cancer is associated with red meat intake and iron toxicity is discussed for one underlying mechanism. Anyhow, for iron itself only limited evidence is found. In this study, effects of different iron compounds on proliferation of HT29 carcinoma and LT97 adenoma human colon cells were investigated. After treatment of cells with inorganic (ferrous sulfate: FeSO₄ and ferric nitrilotriacetate: FeNTA) and organic (hemoglobin and hemin) iron sources (24–72 h), number of cells and metabolic activity were measured. Under normal cell culture conditions, neither iron compound elevated cell growth in either cell line with the exception of FeNTA which induced LT97 cell growth significantly. Distinct inhibition of cell proliferation was measured for organic iron. Serum-free incubation of HT29 cells revealed growth promoting properties of iron under deficiency. Even though organic iron, especially hemin, was a potent growth factor, both substances showed also dose-dependent cytotoxic effects. In conclusion, these data emphasize that not iron itself, but merely organic iron may promote carcinogenic events. Since promotion of proliferation was only detectable under deficiency, cytotoxic properties of organic iron may be of more importance in colon carcinogenesis.     

Mössbauer spectroscopy indicates that iron in an aluminosilicate glass phase is the source of the bioavailable iron from coal fly ash

Iron speciation by M?ssbauer spectroscopy indicates that ferric iron in an aluminosilicate glass phase is the source of the bioavailable iron in coal fly ash and that this iron species is associated with combustion particles, but not with crustal dust derived from soil minerals. Urban particulate has been shown to be a source of bioavailable iron and has been shown to be able to induce the formation of reactive species in cell culture experiments. Crustal dust and laboratory-generated coal fly ash have been studied as surrogates for two sources of metal-bearing particles in ambient air. As much as a 60-fold difference in the amount of iron mobilized by the chelator citrate was observed between fly ash and crustal dust samples with similar total iron contents. The extent of iron mobilization by citrate in vitro has been shown to correlate with indirect measures of excess iron in cultured cells and with assays for reactive oxygen species generation in vitro. M?ssbauer spectroscopy of coal fly ash, before and after treatment with the chelator desferrioxamine B, showed that the iron in an aluminosilicate glass phase was preferentially removed. The removal of the glass-phase iron greatly reduced the amount of iron that could be mobilized by citrate and prevented the particles from inducing interleukin-8 in cultured human lung epithelial (A549) cells. Ferric iron in aluminosilicate glass is associated with particles formed at high temperatures followed by rapid cooling. The observation that ferric iron in aluminosilicate glass is the source of bioavailable iron in coal fly ash suggests that particles from ambient sources and other specific combustion sources should be examined for the presence of this potential source of bioavailable iron.     

Iron deficiency. Misunderstood, misdiagnosed and mistreated

Iron deficiency is a common medical problem that may present in a variety of ways to the general practitioner or the specialist. An understanding of iron physiology is relevant to diagnosis and treatment of iron deficiency. Human iron metabolism is a system based on conservation. For this reason, the most common cause of iron deficiency is loss of the normal conservation of iron and this usually means blood loss. The important implication is that the search for the cause of iron deficiency will usually focus on the gastrointestinal tract in males and non-pregnant, non-menstruating females. Iron deficiency is commonly misdiagnosed. The usual error is misinterpretation of the laboratory features of the anaemia of chronic disease. The serum iron is low, but the iron binding capacity is normal and ferritin is normal or high. There are problems and exceptions involved in interpretation of iron indices. Treatment of iron deficiency requires an understanding of iron absorption and the ability of the marrow to respond. In most circumstances, iron deficiency will respond to adequate doses of oral iron; however, there are a few situations when oral iron is unsuitable and parenteral iron is required. An inadequate response to iron may indicate inadequate supply of iron to the bone marrow (e.g. malabsorption, non-compliance) or failure of the marrow to respond (e.g. concomitant folate deficiency). Pregnancy is a special situation in which conservation of iron is overcome by fetal iron requirements and in which application of the knowledge of iron physiology should be applied to prevent and treat iron deficiency.     

Clinical case reports raise doubts about the therapeutic equivalence of an iron sucrose similar preparation compared with iron sucrose originator

Intravenous iron sucrose has been used to treat iron deficiency and iron deficiency anaemia associated with different chronic diseases for several decades. Despite the complex structure of iron sucrose, copies called iron sucrose similars (ISSs) have been approved according to the generic approach and therefore, therapeutic equivalence is taken for granted. In February 2011, three patients who previously tolerated well the prescribed iron sucrose originator experienced urticaria, oedema and headache within 1 hour after infusion of an ISS that had been substituted for the originator at the pharmacy level. One patient collapsed due to severe hypovolaemic dysregulation and required hospitalisation. Due to emerging evidence that ISSs differ from the iron sucrose originator in safety and efficacy profiles, it seems prudent for physicians as well as patients who require intravenous (i.v.) iron to have available data on therapeutic equivalence of new ISS preparations versus the originator. This may be especially important in patients who are chronically ill and need iron supplementation on a regular, long-term basis.