title: The iron-based phosphate binder PA21 has potent phosphate binding capacity and minimal iron release across a physiological pH range in vitro.
abstract: OBJECTIVE
  Hyperphosphatemia in advanced chronic kidney disease (CKD) necessitates the use of phosphate binders. This in vitro study assessed phosphate binding and Fe release properties of the novel iron-based phosphate binder PA21.
  
  
  METHODS
  Phosphate adsorption and Fe release were assessed under conditions simulating administration of PA21 on an empty stomach and full stomach across a pH range to which PA21 would be exposed during passage through the gastrointestinal (GI) tract.
  
  
  RESULTS
  PA21 showed a robust phosphate binding capacity over the entire physiologically relevant pH range. The high binding capacity at low pH indicates that phosphate binding could begin in the stomach. Under the current experimental setting, the maximal bound phosphate to Fe ratio was 0.47 mmol P/mmol Fe. The largest amount of Fe release was observed at the lowest pH without phosphate and was much lower in the presence of phosphate. These results are in line with the formation of iron phosphate at low pH, as indicated by X-ray photoelectron spectroscopy and thermodynamic calculations. Fe release was minimal (≤ 0.35%) across pH 2.5 - 8.5.
  
  
  CONCLUSIONS
  These studies demonstrate that PA21 has potent phosphate binding capacity and low iron release over a physiologically relevant pH range in the GI tract. These features indicate PA21 could be an effective alternative phosphate binder for CKD patients.
authors.affiliation: Vifor (International) Inc., St. Gallen, and Vifor Pharma, Glattbrugg, Switzerland.
authors.forename: Maria
authors.initials: M
authors.lastname: Wilhelm
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gaillard
authors.forename: Viatcheslav
authors.initials: V
authors.lastname: Rakov
authors.forename: Felix
authors.initials: F
authors.lastname: Funk
mesh_terms: D005290:Ferric Compounds / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D054559:Hyperphosphatemia / Q000188:drug therapy* / Q000209:etiology; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000628:therapy; D013816:Thermodynamics
chemical_list: D005290:Ferric Compounds; C552479:PA21 compound; D007501:Iron