Structure/histotoxicity relationship of parenteral iron preparations

Commercial iron preparations with different chemical structures and stabilities which are indicated for parenteral application were analyzed. After intravenous application in mice, toxic effects were screened by histological examination of liver, kidney, adrenal, lung and spleen. The various iron complexes were classified into four groups according to their physicochemical properties (molecular mass, kinetic and thermodynamic stability). It was found that the toxic effects can be forecasted by the chemical properties. The results clearly show that not all iron preparations tested can be recommended for intravenous application. After injection, the ideal iron preparation is deposited in the reticulo-endothelial system, and not in the parenchyma of the liver, nor mainly in the periportal area. Furthermore, its renal elimination rate should be below 1% of the dose, and there should be practically no iron detectable in the tubuli. The molecular mass of an optimal product is between 30,000 and 100,000 Daltons, and the preparation does not contain any slowly degradable biopolymers, so that the incidence of allergic side effects is reduced to a minimum. Iron preparations consisting only of weak iron complexes, which liberate iron ions stochastically, should not be used for intravenous application.