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PubMed1984

Iron pharmacokinetics after administration of ferric-hydroxide-polymaltose complex in rats.

This paper reports a study of the pharmacokinetics of ferrous sulphate and ferric-hydroxide-polymaltose complex (Hw 6400, Ferrum Hausmann) administered orally and intravenously to anaemic and non-anaemic rats of both sexes. Radiolabelled ferrous sulphate and ferric-hydroxide-polymaltose complex was used to study iron utilization after oral administration. Measurements of radioactivity in serum, packed red cells, whole blood, liver, kidney, spleen, bone and in some cases in the gastrointestinal tract were made following a range of dosages between 0.84 and 41.9 mg Fe/kg. No significant difference in bioavailability or iron utilization was found between the two iron preparations. Pharmacokinetic measurements following i.v. administration showed different distribution volumes, iron clearance and elimination constants for the two preparations. This difference in pharmacokinetic behaviour following oral administration, particularly in the case of non-anaemic rats, was confirmed by the observation that a 10- to 20 fold smaller dose of FeSO4 than of iron-polymaltose complex was required to achieve the same rise in serum iron. It is therefore not justifiable to draw conclusions about the bioavailability of chemically different iron preparations (iron salts and iron hydroxide complexes) on the basis of AUC values for serum iron increases observed in non-anaemic animals or human subjects.

Administration, Oral↗
PubMed1999

Cerebellar granule cells acquire transferrin-free iron by a carrier-mediated process.

In this study, the mechanism of transferrin-free iron uptake by brain neuronal cells was investigated using the cultured cerebellar granule cells. Effects of incubation time, iron concentration, temperature and other divalent metals on the cellular uptake were determined. After five days of plating, the cells were incubated with different concentrations of transferrin-free iron in isotonic sucrose solution at different temperatures for a certain time. The cellular transferrin-free iron uptake was analysed by measuring the cellular radioactivity with a gamma-counter. The result showed that the cultured cerebellar granule cells had the capacity to acquire transferrin-free iron at pH 6.5, at which it was demonstrated that transferrin binds iron very poorly and only very little transferrin can be internalized by reticulocytes and HeLa cells. The iron uptake by cells increased with incubation time in a linear manner at a rate of 0.1076 pmol/microg protein/min within the first 10 min. The uptake was time- and temperature-dependent, iron concentration saturable, and inhibited by several divalent metal ions, such as Co2+, Zn2+, Mn2+ and Ni2+. These characteristics of transferrin-free iron uptake by the cultured cerebellar granule cells observed in this study, similar to those obtained from cells outside of the brain, implied that a carrier-mediated iron transport system might be present on the membrane of this type of brain neuronal cells. In addition, no significant difference in malondialdehyde measurement was found when the cells were incubated without or with the lower concentrations of iron (< 4 microM) for 20 min at 37 degrees C, demonstrating that this system was valid for studying membrane iron transport in this type of brain neuronal cell.

Animals↗
PubMed1984

On the absorption of divalent and trivalent iron in living rats.

For therapeutic purposes ferric and ferrous iron seems to be evaluated in favour of the latter, despite of the fact that at least in animal experiments no difference was observed as far as the bioavailability of either valency state of iron is concerned; prerequisite is that iron has been administered in ionized form. These results have been proven actually by the studies on normal and iron-deficient rats in vivo fed by stomach tube with radioactively labeled 59Fe-(FeSO4), 59Fe-(FeCl3), and the organic complex of 59Fe-Fe(III)-polymaltose). At least in iron-deficient rats the utilization of iron administered in the form of the organic complex was little less than that obtained after having fed FeSO4. Besides the retention of 59Fe-radioactivity 6 days later after the administration also the uptake of 59Fe-radioactivity into erythrocytes and liver has been measured.

Absorption↗
PubMed1982

Deferoxamine mesylate enhancement of 67Ga tumor-to-blood ratios and tumor imaging.

To improve the tumor-to-blood ratio in 67Ga tumor imaging, the effect of administration of deferoxamine mesylate (DFO) was evaluated. DFO improved 67Ga tumor-to-blood ratios in tumor-bearing rats. Administration of DFO 12 h after 67Ga injection did not decrease the concentration of radioactivity in the tumor of rats, but administration of DFO 4 h after 67Ga decreased the concentration of radioactivity in the tumor. Serum unsaturated iron binding capacity in rats was transiently increased by DFO administration, but when DFO was administered before 67Ga injection the tumor uptake showed rather decreased levels. In human studies, DFO accelerated the excretion of 67Ga from the blood, but tumor images were not necessarily improved.

Animals↗
PubMed1996

An improved animal model for studying desferrioxamine.

A hamster model has been developed for studying desferrioxamine. The hamster shows many similarities to man in terms of plasma stability and metabolites formed from desferrioxamine. The [59Fe]ferritin derived from rats has been shown to be sequestered into liver parenchymal cells when injected intravenously into hamsters. The technique has proved sufficiently sensitive to enable detection of differences of < 1% of the radioactivity administered in the elimination of iron. Alterations in iron excretion were seen when dosing desferrioxamine via different routes. The principal route of iron excretion was into the intestines. The effectiveness of the dosing routes for desferrioxamine in removing iron were subcutaneous (10.5%) > intravenous (6.25%) > oral (3.66%) > control (2.19%). A dose-response relationship was demonstrated using the intravenous dose route. The model offers a simple method for comparing the efficacy of administration routes for determining the optimal use of desferrioxamine.

Animals↗