Chemical reactivity of aluminium-based pharmaceutical compounds used as phosphate-binders.
Several aluminium-containing substances, including antacids used as phosphate-binders in treating renal failure, have been analysed in-vitro under different pH conditions for the release of Al3+ ions and for binding of phosphate. Control experiments on different forms of pure aluminium hydroxide validated the methods. At pH 2 it was the most amorphous forms which released Al3+ most rapidly. These aluminium ions, available for absorption by the patient, were released from all antacids tested, but no firm phosphate-binding was detected while the pH remained at 2. Phosphate was bound at pH 8, by adsorption onto the surface of aluminium hydroxide. No significant amounts of free Al3+ exist in solution at pH 8, since at that pH aluminium hydroxide is precipitated. The most amorphous forms of this solid were the most efficient phosphate-binders. Alumino-silicate salts require prior exposure to acid to produce free Al3+ before they can act as phosphate-binders, whereas amorphous aluminium hydroxide acts as an efficient phosphate-binder without prior exposure to acid. Chemical principles are employed to show why aluminium release and phosphate-binding are separate and independent processes. Methods are proposed for maximizing the activity of phosphate- binders in-vivo, while minimising aluminium release.
Cargill
R W
RW
Department of Molecular and Life Sciences, Dundee College of Technology, UK.
Dutkowskij
M
M
Prescott
A
A
Fleming
L W
LW
Stewart
W K
WK
D000535:Aluminum / Q000032:analysis*; D000536:Aluminum Hydroxide / Q000032:analysis; D002626:Chemistry, Pharmaceutical; D006863:Hydrogen-Ion Concentration; D010710:Phosphates / Q000032:analysis*
D010710:Phosphates; D000536:Aluminum Hydroxide; D000535:Aluminum