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Diaminobutane (DAB) Dendrimers Are Potent Binders of Oral Phosphate
Author(s) -
Williams Katie B,
Barycka Katarzyna,
Zella Julia B,
DeLuca Hector F
Publication year - 2009
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.080819
Subject(s) - phosphate , phosphorus , chemistry , phosphate binder , kidney disease , absorption (acoustics) , dialysis , dendrimer , in vivo , secondary hyperparathyroidism , toxicity , oral administration , hyperphosphatemia , pharmacology , medicine , endocrinology , biochemistry , parathyroid hormone , calcium , biology , microbiology and biotechnology , organic chemistry , physics , acoustics
Reduction of blood phosphorus is a critical component in the management of secondary hyperparathyroidism in chronic kidney disease patients. In addition to dialysis treatment and dietary phosphorus restriction, oral phosphate binders are often consumed with meals to reduce the availability of food phosphorus. Several oral phosphate binders are approved for use in chronic kidney disease patients, but all have practical limitations because of toxicity, poor efficacy, or high cost. Using an in vivo method to measure intestinal phosphate absorption in rats using radiolabeled phosphate, we found that first‐, second‐, third‐, and fifth‐generation diaminobutane dendrimer compounds, DAB‐4‐Cl, DAB‐8‐Cl, DAB‐16‐Cl, and DAB‐64‐Cl, respectively, drastically reduce the absorption of inorganic phosphate in a dose‐dependent manner. To avoid complications of metabolic acidosis caused by hydrochloride salts, an acetate salt, DAB‐9‐AcOH, was prepared and shown to be equally effective at binding radiolabeled phosphate as DAB‐8‐Cl. DAB‐8‐AcOH was further shown to increase fecal phosphorus and decrease serum phosphorus in a dose‐dependent manner when fed to rats. These data suggest that dendrimer compounds are of great potential use in the binding of food phosphate for the management of hyperparathyroidism secondary to chronic kidney disease.