THE ROLE OF COMPLEXATION IN THE GASTROINTESTINAL ABSORPTION OF ALUMINUM
Abstract
Aluminum complexation and chelation are shown to significantly affect the solubility, partitioning, and absorption of aluminum. Complexation of aluminum with inorganic bridging ligands results in the formation of insoluble aluminum precipitates. Chelation of aluminum by organic molecules such as alpha hydroxy substituted carboxylic acids may result in the formation of an aluminum complex species which remains in solution at pH levels which mimic those found in the intestinal tract. A number of chelating ligands commonly present in the diet which form soluble complexes with aluminum are identified. Unchelated aluminum species partition into an ethyl acetate phase only at low pH, such as that found in the gastric lumen. Aluminum chelated with a model ligand, citric acid, partitions into ethyl acetate to a significantly greater extent, not only at gastric pH levels, but also at pH levels such as those found in the intestinal lumen. In situ rat gut perfusions at pH 6.0 with commercial amorphous aluminum hydroxide and freshly precipitated amorphous aluminum hydroxide containing perfusates do not elevate plasma aluminum levels. Perfusions with citrate chelated aluminum at pH 6.0 result in significant increases in plasma aluminum levels. Perfusions at pH 8.0 with freshly precipitated amorphous aluminum hydroxide containing perfusates do not elevate plasma aluminum levels. Perfusions with citrate chelated aluminum at pH 8.0 result in significant increases in plasma aluminum levels. Absorption of citrate chelated aluminum from the in situ rat gut at pH 4.0 follows apparent first-order kinetics. Significant absorption of unchelated soluble aluminum cations at pH 4.0 is found only at high perfusate aluminum levels. The aluminum precipitate formed in vivo in the in situ intestinal segment is identified by infrared spectroscopy as an amorphous aluminum hydroxy carbonato-phosphate. The apparent volume of distribution of citrate chelated aluminum in the rat is found to be 92.04 mL/Kg. Absorption rate constants calculated by both initial rates and computer modeling are in good agreement. The absorption rate constant is significantly elevated at pH 6.0, where the anionic chelate species predominates.
Degree
Ph.D.
Subject Area
Pharmaceuticals
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