Diaminobutane (DAB) dendrimers are potent binders of oral phosphate.
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.
Williams
Katie B
KB
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, Madison, Wisconsin 53706-1544, USA.
Barycka
Katarzyna
K
Zella
Julia B
JB
DeLuca
Hector F
HF
D000284:Administration, Oral; D000818:Animals; D002073:Butanes / Q000737:chemistry / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D050091:Dendrimers / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006961:Hyperparathyroidism / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism; D008297:Male; D028044:Phosphate-Binding Proteins / Q000737:chemistry; D010710:Phosphates / Q000737:chemistry* / Q000378:metabolism; D010758:Phosphorus / Q000097:blood* / Q000737:chemistry; D011073:Polyamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000069603:Sevelamer
D002073:Butanes; D002614:Chelating Agents; D050091:Dendrimers; D028044:Phosphate-Binding Proteins; D010710:Phosphates; D011073:Polyamines; D010758:Phosphorus; D000069603:Sevelamer