Sevalamer Hydrochloride, Sevelamer Carbonate and Lanthanum Carbonate: In Vitro and In Vivo Effects on Gastric Environment : Phosphate Binders on Gastric Environment

Abstract

Hyperphosphatemia is common in patients with chronic renal failure. Phosphate binders are associated with gastric intolerance, representing the main reason of drug discontinuation. The aim of this study was to compare the effects in vitro and in vivo of sevelamer hydrochloride (SH), sevelamer carbonate (SC) and lanthanum carbonate (LC) on gastric microenvironment. We have also evaluated the efficacy and tolerability of these drugs in hemodialysis (HD) patients. In vitro analysis: Dissolution time, ability to uptake phosphorus, changes in pH starting from gastric milieu and the amount of carbon dioxide (CO(2)) produced were the variables analyzed. In vivo analysis: 24-h esophago-gastric pH measurement was evaluated in 24 HD patients treated with phosphate binders and proton pump inhibitor (PPI). In vitro: LC dissolved over a longer time compared with SC (58 ± 2.4 vs. 12 ± 0.6 min; P < 0.001) and SH (58 ± 2.4 vs. 10.3 ± 0.8 min; P < 0.001), determining the most alkaline pH. SC had the highest chelation power, binding 4.00 × 10(-9)  mol/L of phosphoric acid. CO2 volume released was increased in LC solution (53.2 ± 7.8) compared to SC (33.9 ± 6.2; P < 0.001) and SH (2.3 ± 1.8; P < 0.001). In vivo: gastric pH increased after administration of phosphate binder. The most alkaline pH was recorded in patients treated with SC. The alkalinization of the gastric environment was not prevented by PPI therapy. 424 episodes of esophageal reflux were registered, 74% of them were alkaline. The LC group was characterized by the highest number of episodes. Sevelamer carbonate had a greater capacity and rapidity to chelate phosphorus, with a mild tolerability, due to its low CO(2) production. Sevelamer HCl was the most tolerated chelator because it did not produce CO(2), while lanthanum carbonate was the least soluble.