Inulin-iron complexes: a potential treatment of iron deficiency anaemia.

The aim of this work was that to synthesize macromolecular derivatives based on inulin able to complex iron and useful in the treatment of iron deficiency anaemia. Carboxylated or thiolated/carboxylated inulin derivatives were obtained by single or double step reactions, respectively. The first one was obtained by reaction of inulin (INU) with succinic anhydride (SA) alone obtaining INU-SA derivative; the second one was obtained by the reaction of INU with succinic anhydride and subsequent reaction of INU-SA with cysteine; both derivatives were treated with ferric chloride in order to obtain the INU-SA-Fe(III) and INU-SA-Cys-Fe(III) complexes. Both complexes showed an excellent biodegradability in the presence of inulinase and pronounced mucoadhesion properties; in particular, thiolated derivative INU-SA-Cys showed greater mucoadhesive properties than polyacrylic acid chosen, as a positive reference polymer, and a good iron release profile in condition mimicking the intestinal tract. These results suggest the potential employment of such systems in the oral treatment of iron deficiency anaemia or as supplement of iron in foods.     

Ferric trimaltol corrects iron deficiency anaemia in patients intolerant of iron

Background:

Oral iron supplements, which are usually in the form of ferrous (Fe²⁺) salts, are toxic to the gastrointestinal mucosa, and so intolerance is common, resulting in poor compliance and failure of treatment. The sugar derivative maltol strongly chelates iron, rendering it available for absorption and stabilized in the less toxic ferric (Fe³⁺) form.

Aim:

To test whether ferric trimaltol could correct iron deficiency anaemia in patients intolerant of ferrous sulphate.

Methods:

Twenty-three patients were recruited from gastroenterology clinics, of whom 15 had inflammatory bowel disease, a group often difficult to treat with oral iron. Patients with iron deficiency anaemia and documented intolerance to ferrous sulphate were given 3 months of treatment with ferric trimaltol.

Results:

Nineteen of 23 patients completed the treatment and anaemia was fully corrected in 14 of these, mean haemoglobin increased from 106 ± 15 to 126 ± 16 g/L, and there was a particularly low incidence of side-effects. Of 11 patients with inflammatory bowel disease who completed the study, nine fully corrected their anaemia.

Conclusion:

The results demonstrate that in patients intolerant of ferrous compounds, ferric trimaltol corrects iron deficiency and has a low incidence of side-effects.

     

Effect of iron deficiency anaemia and its treatment on sulphadimidine absorption

Summary The effect of iron deficiency anaemia and its treatment on the absorption of sulphadimidine has been investigated in adult patients.The absorption judged by total % of the dose excreted in urine and C_max, t_max, AUC and Kabs in plasma, was not significantly different before and after iron therapy or correction of anaemia.However, sulphadimidine absorption by the anaemic patients was significantly greater than in normals.     

A prevalence survey of iron deficiency and iron deficiency anaemia in pregnant and lactating women, adult males and pre-school children in Zimbabwe

OBJECTIVE: To determine the prevalence of iron deficiency and iron deficiency anaemia (IDA) in selected population groups in Zimbabwe. DESIGN: The study was a cross sectional, household prevalence survey. A structured questionnaire was used to interview study participants to elicit information on risk factors associated with iron status and IDA. Blood samples were collected for quantitative measurement of ferritin in serum and haemoglobin estimation as part of a full blood count. SETTING: The study was conducted in four administrative provinces of the country, Mashonaland Central, Midlands, Matebeleland South and Matebeleland North covering three of the five agro-ecological regions of the country. Thirty clusters were randomly selected from 28 enumeration districts. SUBJECTS: The multistage sampling technique was applied. The total sample consisted of 3,151 study participants made up of 746 pregnant women, 800 lactating women, 811 adult males and 799 pre-school children. Up to 202 results could not be used in the analysis. MAIN OUTCOME MEASURES: R Stoltzfus, emphasizes that haemoglobin concentration is the key indicator for IDA surveillance. Serum ferritin levels measured against 10 ng/dl for females and 15 ng/dl for males as standards below which there is IDA. Serum ferritin levels of over 300 ng/dl above which there is iron overload. Haemoglobin levels were based on the World Health Organisation standards of 11 g/dl below which pregnant women and preschool children were considered to have IDA, 13 g/dl for adult males and 12 g/dl for lactating women. The proportion of individual households with protected water supplies, sanitation and levels of education as they influence the prevalence of IDA. Dietary habits with regards their influence on iron availability. RESULTS: The overall prevalence of IDA was 24.1% of the total study sample. Of the preschool children surveyed 17.7% had IDA, 33.0% of pregnant women, 29.6% of lactating women and 16.5% of adult males had IDA. Of the population 9.1% surveyed had evidence of iron depletion on the basis of serum ferritin levels. More of the pregnant women had iron depletion, 14.8%, compared to adult males with 2.2%. Individuals in regions IV and V were much more affected by iron depletion and IDA than their counterparts in regions II and III in this study. CONCLUSION: Iron deficiency anaemia (IDA) is a problem of public health significance in Zimbabwe and is associated with areas of food insecurity. From a policy perspective the prevention and control of IDA should be a priority on national nutrition and health agenda.     

Effect of iron deficiency anaemia and its treatment on single dose phenytoin bioavailability

Summary Iron deficiency is a common nutritional deficiency, which leads to structural functional and enzymatic changes in the body that may affect the pharmacokinetics of drugs.The present study in 7 normal volunteers and 8 adult male patients with irondeficiency anaemia (IDA) was done to investigate the effect of iron deficiency and its treatment with total dose iron (TDI) on the bioavailability of a single dose of phenytoin. Phenytoin bioavailability was investigated before and 3 and 28 days after TDI.The bioavailability parameters C_max, t_max, AUC and 2 h phenytoin concentrations were not significantly different in anaemic patients as compared to normal volunteers before or after treatment, except for an increase in t_max 28 days after TDI treatment.     

Effect of iron deficiency anaemia and its treatment on the absorption and elimination of phenformin

1. The extent of phenformin absorption and its rate of urinary excretion have been assessed in adult patients with iron deficiency anaemia, a condition which compromises gastrointestinal function. 2. Phenformin (100 mg) was administered orally to patients before treatment, three days after the start of a course of iron treatment (oral 300 mg b.d. or total intravenous iron) and at the end of 28 days, when haemoglobin was over 10 gm%. 3. No significant difference was found between mean total amounts of phenformin and 4-hydroxyphenformin excreted in urine, before treatment or after 3 or 28 days replacement therapy. It is concluded that phenformin absorption is not affected by iron deficiency. 4. In addition, iron deficiency had no significant effect on phenformin elimination half-life.     

Effect of iron deficiency anaemia and its treatment on the absorption and elimination of phenformin

1.The extent of phenformin absorption and its rate of urinary excretion have been assessed in adult patients with iron deficiency anaemia, a condition which compromises gastrointestinal function.

2.Phenformin (100 mg) was administered orally to patients before treatment, three days after the start of a course of iron treatment (oral 300 mg b.d. or total intravenous iron) and at the end of 28 days, when haemoglobin was over 10 gm%.

3.No significant difference was found between mean total amounts of phenformin and 4-hydroxyphenformin excreted in urine, before treatment or after 3 or 28 days replacement therapy. It is concluded that phenformin absorption is not affected by iron deficiency.

4.In addition, iron deficiency had no significant effect on phenformin elimination half-life.     

Benefit of concomitant gastrointestinal and gynaecological evaluation in premenopausal women with iron deficiency anaemia

Background  Iron-deficiency anaemia (IDA) is common in premenopausal women and menorrhagia is often considered responsible.
Aim  To evaluate prospectively the occurrence of bleeding and iron malabsorption related gastrointestinal (GI) diseases likely responsible of IDA in premenopausal women regardless of their menstrual flow.
Methods  One hundred and eighty-seven premenopausal women [median age 39 (20–56) years] irrespective of their menstrual flow underwent gastroscopy with gastric and duodenal biopsies and faecal occult blood test (FOBT). Patients over 50 years, positive 1st degree family history for colonic cancer and/or positive FOBT underwent colonoscopy too.
Results  Menorrhagia was present in 67.4% of premenopausal women. A possible GI cause of IDA was found in 129/187 patients; in 65.2% the cause of IDA was possibly related to iron malabsorption diseases. GI bleeding as a cause of IDA was found in seven patients. An exclusive GI cause of IDA was found in 26.7% of premenopausal women, whereas a possible GI cause was observed in 34.2% of menorrhagic premenopausal women. The main risk factor for the presence of likely GI causes was the presence of upper GI symptoms (OR 5.2: 95% CI = 1.6–16.4).
Conclusions  Most premenopausal women had a possible upper GI cause of IDA because of diseases related to iron malabsorption. Menorrhagia and a GI cause coexist in one-third of women with iron-deficiency anaemia.     

Prolyl hydroxylase inhibition corrects functional iron deficiency and inflammation-induced anaemia in rats

Background and Purpose

Small-molecule inhibitors of prolyl hydroxylase (PHD) enzymes are a novel target for the treatment of anaemia and functional iron deficiency (FID). Other than being orally bioavailable, the differentiation of PHD inhibitors from recombinant human erythropoietin (rhEPO) has not been demonstrated.

Experimental Approach

JNJ-42905343 was identified and characterized as a novel inhibitor of PHD and its action was compared with rhEPO in healthy rats and in a rat model of inflammation-induced anaemia and FID [peptidoglycan-polysaccharide (PGPS) model].

Key Results

Oral administration of JNJ-42905343 to healthy rats increased the gene expression of cytochrome b (DcytB) and divalent metal-ion transporter 1 (DMT1) in the duodenum, and increased plasma EPO. Repeated administration of JNJ-42905343 for 28 days increased blood haemoglobin, mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV). The serum iron concentration was increased with low doses (0.3 mg·kg⁻¹) but reduced at high doses (6 mg·kg⁻¹). In PGPS-treated rats, administration of JNJ-42905343 for 28 days corrected FID and anaemia, as reflected by increased blood haemoglobin, MCH and MCV. Increased expression of DcytB and DMT1 genes in the duodenum resulting in increased iron availability was defined as the mechanism for these effects. rhEPO did not affect DcytB and DMT1 and was not effective in PGPS-treated rats.

Conclusions and Implications

PHD inhibition has a beneficial effect on iron metabolism in addition to stimulating the release of EPO. Small-molecule inhibitors of PHD such as JNJ-42905343 represent a mechanism distinct from rhEPO to treat anaemia and FID.     

Bioavailability of oral iron drugs as judged by a 59Fe-whole-body counting technique in patients with iron deficiency anaemia. Therapeutic efficacy of iron(II)-glycine sulfate

The bioavailability of the oral iron compound iron(II)-glycine sulfate (ferro sanol duodenal, FSD, 1 x 100 mg Fe/d) was studied in 56 patients with iron deficiency anaemia using a 59Fe-labelling technique and 59Fe-whole-body counting. This technique measures the individual iron loss and allows in patients with substantial blood loss under iron medication a reliable information on the bioavailability of the drug. In all patients, the increased loss of iron (mean 5.8 +/- 4.4 mg/d) was clearly compensated by the iron utilisation (mean: 11.1 +/- 5.6 mg/d) from a daily dosage of 100 mg iron from FSD. A significant increase in the haemoglobin concentration was observed within the monitored treatment period of 6-10 weeks (mean Hb increase from 10.7 +/- 1.7 to 12.1 +/- 1.8 g/dl). FSD has therefore documented a bioavailability of at least 11% from a single daily dose of 100 mg Fe and was effective in the treatment of the anaemia in almost all patients under study.     

Ferumoxytol for treatment of iron deficiency anemia in patients with chronic kidney disease

Background: Iron deficiency anemia (IDA) is a common problem in patients with chronic kidney disease (CKD). Use of intravenous (i.v.) iron effectively treats the resultant anemia, but available iron products have side effects or dosing regimens that limit safety and convenience. Objective: Ferumoxytol (Feraheme^?) is a new i.v. iron product recently approved for use in treatment of IDA in CKD patients. This article reviews the structure, pharmacokinetics, and clinical trial results on ferumoxytol. The author also offers his opinions on the role of this product in clinical practice. Methods: This review encompasses important information contained in clinical and preclinical studies of ferumoxytol and is supplemented with information from the US Food and Drug Administration. Results/conclusion: Ferumoxytol offers substantial safety and superior efficacy compared with oral iron therapy. As ferumoxytol can be administered as 510 mg in < 1 min, it is substantially more convenient than other iron products in nondialysis patients. Although further experience with this product is needed in patients at higher risk of drug reactions, ferumoxytol is likely to be highly useful in the hospital and outpatient settings for treatment of IDA.