The development and in-vitro evaluation of novel mixed metal hydroxy-carbonate compounds as phosphate binders

Abstract

The currently available phosphate binders are relatively inefficient and suffer from clinical side-effects of increased absorption of calcium and aluminium and the diarrhoea-inducing effects of magnesium. A new class of compounds based on mixed metal hydroxides has been developed and evaluated for their potential as phosphate binders. The mixed metal hydroxides were prepared using a standard procedure for hydrotalcite (Al2Mg6(OH)16.CO3.4H2O) by substituting Fe3+ for Al3+, with Mg2+ or Ca2+ as the divalent metal ion. Phosphate precipitation (binding) was examined at different pH values in aqueous solution and in various food mixtures in comparison with hydrotalcite, Al(OH)3, CaCO3 and Mg(OH)2 on the same weight-to-weight basis. A series of compounds with differing ratios of metal ions (Fe:Mg/Ca 1:2 or 1:3) gave analytically similar ratios to those predicted from the initial amounts added. CTFeCa bound > 90% phosphate in aqueous solution compared with 65% binding with CTFeMg, 85% binding with Mg(OH)2, and less than 30% binding for CaCO3 and Al(OH)3. The mixed metal compounds also bound up to 80% phosphate in various food matrices, which was relatively independent of changes in pH, compared with Mg(OH)2, where binding decreased from 85% at pH 3.0 to 25% at pH 8.0. Al(OH)3 and CaCO3 were relatively ineffective phosphate binders under all the conditions tested. The mixed metal hydroxides compounds show considerable promise as phosphate binders over those currently available and warrant further patient-based in-vivo testing.

Influence of pH and phosphate concentration on the phosphate binding capacity of five contemporary binders. An in vitro study

“…CC bound more phosphate in acidic conditions, which is in concurrence with the previous literature, probably because of its optimum solubility in an acidic milieu . Similar effects were demonstrated with concomitant use of pantoprazole and CC in vivo where serum phosphate was higher in the group using both CC and pantoprazole …”

“…Although, in a randomized clinical trial in haemodialysis patients using SH only or SH and pantoprazole, no significant difference between phosphate levels was observed. 13 CC bound more phosphate in acidic conditions, which is in concurrence with the previous literature, 17,23 probably because of its optimum solubility in an acidic milieu. 7 Similar effects were demonstrated with concomitant use of pantoprazole and CC in vivo where serum phosphate was higher in the group using both CC and pantoprazole.…”

Different Mg to Fe Ratios in the Mixed Metal MgFe Hydroxy-Carbonate Compounds and the Effect on Phosphate Binding Compared With Established Phosphate Binders

“…Their use as phosphate binders was first reported in this laboratory. We have previously shown that MMHs based on CaFe and MgFe can bind phosphate in solution 40,41. In the present study, we have investigated further the effect of different Mg 2+ :Fe 3+ ratios and preparations, such as aging and drying, on their phosphate binding performances in order to optimize the product.…”

Novel Therapeutic Options for the Treatment of Mineral Metabolism Abnormalities in End Stage Renal Disease

“…The phosphate-binding capacity of iron was first recognized in experimental and animal studies (21)(22)(23). Iron is a cation that binds phosphate in the NOVEL THERAPEUTIC OPTIONS FOR THE TREATMENT OF MINERAL METABOLISM ABNORMALITIES GI tract and results in increased phosphate excretion in feces.…”