teferrol and Body-Weight

The originator iron polymaltose complex (Maltofer®, IPC, Vifor International, St. Gallen, Switzerland) has been used for over 30 years to treat iron deficiency anemia. Its physico-chemical properties allow for a controlled release of iron, a property which translates into low toxicity and good gastrointestinal (GI) tolerability of the drug compared to the commonly used ferrous salts. A variety of different iron polymaltose complex similars are commercially available with varying structures and, thus, different efficacy and toxicity compared to IPC. In this study, the median lethal dose, the GI tract and liver toxicity of an IPC similar (Vitalix®, IPCSVITA, Laboratorios Roemmers, Buenos Aires, Argentina) were compared with those of IPC in healthy rats.. The median lethal dose of IPCSVITA was determined as the dose required to kill 6 out of 12 rats after 24 h from dosing. To compare the GI and liver toxicities, rats received IPCSVITA or IPC (both 280 mg iron/kg body weight) for 28 days. GI toxicity was assessed macroscopically by scoring lesion severities and microscopically by analyzing the villi/crypt ratio, number of eosinophils/villi and number of Goblet cells/villi. Ferritin was assessed in the small intestine villi and in the liver by immunostaining. Iron deposits in the liver were assessed by Prussian blue staining.. Serum iron concentration and transferrin saturation (TSAT) were significantly higher in the IPCSVITA group vs. the IPC and the control groups. Food consumption, body weight, and bowel movement at Day 29 were significantly lower within the IPCSVITA group vs. the IPC or the control groups. The lesion scores in the stomach and in the lower GI tract of the IPCSVITA group were significantly higher than those of the IPC and control groups. The villi/crypt ratio and the number of Goblet cells/villi in the small intestine were significantly lower in IPCSVITA-treated animals than in IPC-treated or control animals. The number of eosinophils per villi was significantly increased in the IPCSVITA group vs. IPC and control group. In the lower GI tract, microscopic lesions were observed only in the IPCSVITA group. The amount of ferritin in the small intestine and in the liver was higher in IPC-treated animals vs. IPCSVITA- treated or control animals.. Higher serum iron and TSAT levels, lesions in the stomach and lower GI tract suggest the presence of weakly bound iron on the surface of the IPCSVITA complex, which has different physico-chemical properties than IPC. The lower levels of iron deposits in the liver suggest that the iron from IPCSVITA is taken up in a less controlled way than from IPC, thus, potentially accumulating in the wrong cellular compartment.

Topics: Animals; Body Weight; Chemistry, Pharmaceutical; Defecation; Eating; Female; Ferric Compounds; Ferritins; Gastrointestinal Tract; Hematinics; Iron; Lethal Dose 50; Liver; Male; Rats; Rats, Sprague-Dawley; Transferrin

Simple iron salts, such as iron sulphate, often interact with food and other medications reducing bioavailability and tolerability. Iron(III)-hydroxide polymaltose complex (IPC, Maltofer) provides a soluble form of non-ionic iron, making it an ideal form of oral iron supplementation. The physicochemical properties of IPC predict a low potential for interactions. The effects of co-administration with aluminium hydroxide (CAS 21645-51-2), acetylsalicylic acid (CAS 50-78-2), bromazepam (CAS 1812-30-2), calcium acetate (CAS 62-54-4), calcium carbonate (CAS 471-34-1), auranofin (CAS 34031-32-8), magnesium-L-aspartate hydrochloride (CAS 28184-71-6), methyldopa sesquihydrate (CAS 41372-08-1), paracetamol (CAS 103-90-2), penicillamine (CAS 52-67-5), sulfasalazine (CAS 599-79-1), tetracycline hydrochloride (CAS 64-75-5), calcium phosphate (CAS 7757-93-9) in combination with vitamin D3 (CAS 67-97-0), and a multi-vitamin preparation were tested in rats fed an iron-deficient diet. Uptake of iron from radiolabelled IPC with and without concomitant medications was compared. None of the medicines tested had a significant effect on iron uptake. Iron-59 retrieval from blood and major storage organs was 64-76% for IPC alone compared with 59-85% following co-administration with other medications. It is concluded that, under normal clinical conditions, IPC does not interact with these medications.

Topics: Animals; Body Weight; Chelating Agents; Dose-Response Relationship, Drug; Drug Interactions; Ferric Compounds; Hemoglobins; Iron; Iron Deficiencies; Iron Radioisotopes; Male; Rats

Four baboons receiving intramuscular iron for 15 months were compared with two control baboons. From the overall two-year observation period the following data emerge: (1) The baboon is a suitable animal for obtaining a massive and chronic iron overload. Liver iron concentrations reached very high levels (ranging from 41.3 to 180.6 mumol/100 mg dry weight vs 1.7 +/- 0.5, mean +/- SEM, in controls), and a major liver iron overload (ie, with concentration values greater than or equal to 18) was present in all four animals for an average period of 16.5 months (range 14-19). (2) When compared with human hepatic iron-overload disorders, iron distribution was similar to that observed in secondary (transfusional) hepatic siderosis since iron deposits were found primarily in sinusoidal cells. However, a marked parenchymal siderosis was also obtained close to that observed in primary (genetic) siderosis. Iron toxicity was present biologically as indicated by an increase in serum transaminases. Histologically, a slight fibrosis was observed in the most heavily iron-overloaded baboon. On the whole, this study of subhuman primates brings new evidence that iron per se has only a minor hepatic damaging effect. It also suggests that the iron-overloaded baboon liver provides a promising tool for the study of liver cell disturbances in human iron overload.

Topics: Animals; Aspartate Aminotransferases; Body Weight; Disease Models, Animal; Female; Ferric Compounds; Injections, Intramuscular; Iron; Liver; Male; Papio; Time Factors; Tissue Distribution