A preparation containing an iron-poly (sorbitol-gluconic acid) complex for parenteral treatment of iron deficiency anaemia is described. The physical and chemical properties of the iron complex have been studied by using electrophoresis and gel permeation chromatography. A rapid absorption from the injection site after intramuscular administration to rabbits takes place, 70 per cent of the iron being absorbed after 2 4 4 8 hours. Thereafter, the absorption rate is slower, and 32 days after the injection 94 per cent has been absorbed from the injection site. In rabbits the maximum level of iron in serum is reached after 12-24 hours; in dogs after 1-3 hours. Disappearance from the serum takes place slowly. The complex is exclusively absorbed via the lymphatic route. Nine to ten per cent of the given dose is excreted by the kidney within 72 hours in rats and 24 hours in rabbits after intramuscular administration. On administration of the preparation to rats, made anaemic by phlebotomy, a rapid increase of haemoglobin values is observed as well as a very high utilization of the retained amount of the given dose.
The distribution of (59)Fe has been investigated in nonpregnant, pregnant and lactating rats and their young after injection of solutions containing a high molecular weight iron-dextrin complex (iron-dextrin, intravenously), and a low molecular weight complex of iron, sorbitol and citric acid (iron-sorbitol, intramuscularly), each labelled with (59)Fe. At different times after injection of a dose corresponding to 1.5 mg of iron per kg of body weight, the quantity of (59)Fe was determined in different organs, urine and carcass, and for pregnant rats also in foetuses and placentas. In some investigations, distribution in the foetuses was also studied. Iron-dextrin was localized mostly in the livers of both pregnant and nonpregnant rats; (59)Fe was then redistributed from this organ and incorporated into the erythrocytes. In pregnant rats, redistribution was accompanied by a placental transfer, the degree of incorporation into the erythrocytes of the mother being diminished. About 30% of the iron-sorbitol was excreted in the urine, while the remainder was distributed throughout the whole organism. Incorporation into the erythrocytes and placental transfer began earlier with iron-sorbitol than with iron-dextrin. At 14 days from injection into nonpregnant rats, however, the degree of incorporation into the erythrocytes of iron from the two complexes was identical. The rate at which incorporation of (59)Fe occurred into the erythrocytes was the same for the two preparations. The degree of incorporation into the erythrocytes after injection of iron-sorbitol into pregnant rats diminished in the same pattern as for iron-dextrin. Investigations into the mechanism of the placental transfer of iron-sorbitol from mother to foetus suggested that this is essentially an active process.
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