Iron deficiency is the most common nutritional problem worldwide, especially in the developing countries. Oral
iron supplementation programs have failed because of noncompliance and gastrointestinal toxicity, thereby necessitating parenteral administration of
iron. For parenteral administration, only
iron-
carbohydrate complexes are currently used, because monomeric
iron salts release free
iron, thereby causing
oxidant injury. However,
iron-
carbohydrate complexes also have significant toxicity, and they are expensive. We have proposed the hypothesis that monomeric
iron salts can be safely administered by the parenteral route if
iron is tightly complexed to the
ligand, thereby causing clinically insignificant release of free
iron, and the kinetic properties of the compound allow rapid transfer of
iron to plasma
transferrin. A detailed analysis of the physicochemical and kinetic properties reveals that ferric
iron complexed to
pyrophosphate or acetohydroxamate
anions may be suitable for parenteral administration. We have demonstrated that infusion of
ferric pyrophosphate into the circulation via the
dialysate is safe and effective in maintaining
iron balance in patients undergoing maintenance
hemodialysis. Parenteral administration of monomeric
iron compounds is a promising approach to the treatment of
iron deficiency in the general population and merits further investigation.