New phosphate binding agents: Ferric compounds

Several prior studies suggest that ferric compounds bind dietary phosphate and possess clinical potential as phosphate binding agents. Therefore, this study was conducted to measure the effect of several ferric compounds on i ntestinal phosphate binding and absorption. Balance studies lasting 2 to 4 wk were performed in normal and azotemic (achieved by subtotal nephrectomy) rats maintained on a 1.02% phosphorus diet supplemented with ferric salts (formulated to 0.95% Fe) or no ferric salt (control). In rats with normal r enal function (average creatinine clearance, 4.0 ml/min per kg), the averag e net intestinal absorption of phosphate over all balance periods was 103.3 mg/d for the control group versus 84.7 mg/d for the ferric citrate group ( P < 0.005). In the azotemic rats (average creatinine clearance, 3.3 ml/min per kg), the average net intestinal absorption of phosphate over all balanc e periods was significantly lower for the three ferric groups than the cont rol groups (P less than or equal to 0.02): 95.3 mg/d for the control group versus 75.6 mg/d for the ferric ammonium citrate-treated group (P = 0.058), 77.0 mg/d for the ferric citrate-treated group (P 0.057), and 62.5 mg/d fo r the ferric chloride-treated group (P < 0.002). Urinary phosphate excretio n fell, sometimes to an even greater extent than did intestinal absorption, yielding no net reduction in phosphate balance in these growing, young ani mals with relatively preserved renal function. Calcium balance was largely unaffected by the ferric compounds. There were trends toward decreased seru m phosphorus and parathyroid hormone concentrations and increased iron and hematocrit in the ferric-treated azotemic groups. All tested ferric compoun ds were well tolerated, but animal growth was stunted in the ferric chlorid e animals compared with the control group. Phosphate binding was estimated at 85 to 180 mg per gram of elemental iran, which is comparable to other ph osphate binding agents. Ferric salts decrease net intestinal phosphate abso rption and hold promise for the treatment of phosphate retention in patient s with renal failure.