Sevelamer and Other Anion-Exchange Resins in the Prevention and Treatment of Hyperphosphataemia in Chronic Renal Failure

Abstract

Sevelamer, or more precisely ‘sevelamer hydrochloride’, is a weakly basic anion-exchange resin in the chloride form that was introduced in 1997 for the treatment of the hyperphosphataemia of patients with end-stage renal failure, usually those on long-term haemodialysis. The rationale for this therapy was that sevelamer would sequester phosphate within the gastrointestinal tract, so preventing its absorption and enhancing its faecal excretion. Over the succeeding years, large numbers of patients have been treated with sevelamer, and it has fulfilled expectations in helping to control the hyperphosphataemia of end-stage renal failure. However, it is only one of many anion-exchange resins that could be used for this purpose, some of which are currently available for clinical use and are much less costly than sevelamer. Theoretical considerations suggest that some of these other resins might be at least as efficient as sevelamer in sequestering phosphate in the gastrointestinal tract. Neither sevelamer, nor any of these other agents, has been submitted to a proper metabolic balance study to measure the amount of phosphate sequestered by the resin in the bowel, and without this information it is impossible to judge which is the ideal resin for this purpose.

Phosphate homeostasis and the renal-gastrointestinal axis

“…If confirmed, this observation could have implications for the effectiveness of phosphate binders in CRF. The high levels of short-chain fatty acids normally present in the colonic lumen would be expected to displace phosphate from the anion exchanger binding sites and make it available for absorption (144), potentially negating any upstream benefit of binders on phosphate balance. PiT1 protein has been localized to the BBM of enterocytes in the rat duodenum and jejunum, with the highest levels found in the jejunum.…”

Evaluation of the In Vitro Efficacy of Sevelamer Hydrochloride and Sevelamer Carbonate

“…12,13 Non-calcium-based phosphate binding agents including sevelamer hydrochloride, sevelamer carbonate, and lanthanum carbonate have also been shown to be effective in the prevention and treatment of hyperphosphatemia in patients with ESRD. [14][15][16][17][18][19] Sevelamer hydrochloride is a cationic, polymeric ionexchange resin derived from poly(allylamine hydrochloride) crosslinked with epichlorohydrin in which forty percent of the amines are protonated. As shown in Figure 1, the amines in sevelamer hydrochloride can bind phosphate anions through ion exchange and hydrogen bonding to form insoluble, nonabsorbable sevelamer-phosphate complexes, which are subsequently eliminated via the feces.…”

“…This presents a risk of sevelamer hydrochloride-associated metabolic acidosis. 16 Therefore, sevelamer carbonate has been developed as an improved, buffered form of sevelamer. Similar to sevelamer hydrochloride, sevelamer carbonate is an anion-exchange resin with the same polymeric structure as that of sevelamer hydrochloride, but with carbonate replacing chloride as the anion (see Fig.…”

Adsorption of cefotaxime sodium salt on polymer coated ion exchange resin microparticles: Kinetics, equilibrium and thermodynamic studies

“…More recently they have been used in pharmaceutical and medical fields for isolation and purification of pharmaceutical active ingredients (Belakhov & Momot, 1983) or as functional excipients in dosage form (taste masking agent, tablet disintegrant, drug stabilization agent and sustained release agent) and or active drug ingredients. From a therapeutic standpoint it is well known that colestipol (a weakly basic ion exchange resin), cholestyramine (a strongly basic ion exchange resin) and colesevelam act as cholesterol reducers (Angelin & Einarsson, 1981), Kayexalate (sodium polystyrene sulfonate) is approved for use in the treatment of hyperkalemia (Sterns, Rojas, Bernstein, & Chennupati, 2010), sevelamer (weakly basic anion exchange resin in the chloride form) is used for the management of hyperphosphataemia in chronic renal failure (Wrong & Harland, 2007) and nicorette gum, a product based on anionic exchange resin is used in smoking cessation programs (Conaghey, Corish, & Corrigan, 1998).…”