Relative in Vitro Efficacy of the Phosphate Binders Lanthanum Carbonate and Sevelamer Hydrochloride

• Published in: Journal of pharmaceutical sciences 2007-10, Vol.96 (10), p.2818-2827
• Main Authors: Autissier, Valerie, Damment, Stephen J.P., Henderson, Richard A.
• Format: Article
• Language: English
• Subjects: adsorption; Anions; Bile Acids and Salts - chemistry; Binding, Competitive; Biological and medical sciences; Chelating Agents - chemistry; Chelating Agents - metabolism; Drug Stability; General pharmacology; Hydrogen-Ion Concentration; in vitro models; Kinetics; Lanthanum - chemistry; Lanthanum - metabolism; Medical sciences; Models, Chemical; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Phosphates - chemistry; Phosphates - metabolism; Polyamines - chemistry; Polyamines - metabolism; protein binding; Sevelamer; targeted drug delivery; transcellular transport
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.20956

The high tablet burden and poor compliance associated with phosphate‐binding drugs has led to a search for more potent agents. In vitro‐binding studies were performed on the recently introduced binder, lanthanum carbonate (LC; Fosrenol®), to compare its phosphate‐binding affinity with sevelamer hydrochloride (SH; Renagel™). Langmuir equilibrium binding affinities (K1) for LC and SH were established using different phosphorus (5–100mM) and binder (134–670mg per 50 mL) concentrations at pH 3–7, with or without salts of bile acids present (30mM). At all pH levels, LC had a higher binding affinity for phosphate than SH. For LC, K1 was 6.1 ± 1.0mM−1 and was independent of pH. For SH, K1 was pH dependent, being 1.5 ± 0.8mM−1 at pH 5–7 and 0.025 ± 0.002mM−1 at pH 3, that is, >200 times lower than for LC. In the presence of 30mM bile salts, SH lost 50% of its phosphate, whereas no displacement of phosphate occurred for LC. These findings indicate that LC binds phosphate more effectively than SH across the pH range encountered in the gastrointestinal tract, and has a lower propensity for bound phosphate to be displaced by competing anions in the intestine. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2818–2827, 2007