Chelating agents in the drug dosage design of iron preparations Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/mp48sj33b

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  • The role of iron in the body is well known for it is a component of hemoglobin, myoglobin, cytochrome, enzyme catalase and peroxidase. Iron deficiency anemia is widespread among vulnerable groups in industrialized societies and in the general population of tropical developing areas. In the United States there are ten million women with no iron reserves to meet the physiological needs of menstruation and pregnancy. The normal diet has five times the total amount of needed to maintain iron balance but, unfortunately, less than ten percent is absorbed. The absorption of iron has been increased by combining it with reducing agents such as ascorbic acid. Also it was found that protein uptake is necessary for adequate iron absorption. Increase in absorption was noted when iron was combined with chelating agents. It was suggested that these chelating agents bind iron strongly, forming a stable ring complex which seems to be necessary to maintain it in a soluble and permeable form. The purpose of this thesis research was to determine the effect of amino acids on iron absorption. The amino acids were glycine, 1. proline, d.1. tryptophan, 1. asparagine, d.1. alanine, d.1. phenylalanine, d.1. leucine, serine, d.1. methionine, and 1. isoleucine. Ferrous sulphate was combined with each of the amino acids in a molar ratio of 1:2. Iron-59 was used as a tracer. At various time periods after oral administration to rats, blood samples were collected from the rats' toes. At the end of four hours, the animals were sacrificed and liver, kidney, muscle, heart and brain samples were taken from the animals. All blood and organ samples were counted using a solid scintillation counter. All amino acids increased iron absorption, but the increase was most notable in asparagine, and then glycine. No correlation was found between stability constants of iron with amino acids and initial rate of absorption or area under the curve. In the organs, iron was found mostly in the liver. Lesser amounts were found in the heart and kidney, and very small amounts in the muscle and brain. Glycine - iron and control tablets were prepared using the direct compression method. Glycine was chosen rather than asparagine because it is much cheaper. These tablets were activated in the OSU TRIGA Reactor for four hours with a neutron flux of 3x10¹² neutron/cm² /sec. These tablets were administered to groups of four rabbits. Blood samples were collected from their ears using the same sampling times as for rats. At the end of four hours the animals were sacrificed and organ samples were taken from the animals. All these samples were counted as before. Results were analyzed using PROPHET¹ and show that iron is absorbed much better when administered with glycine than when administered alone.
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