Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2485890 | Journal of Pharmaceutical Sciences | 2007 | 10 Pages |
Abstract
The high tablet burden and poor compliance associated with phosphateâbinding drugs has led to a search for more potent agents. In vitroâbinding studies were performed on the recently introduced binder, lanthanum carbonate (LC; Fosrenol®), to compare its phosphateâbinding affinity with sevelamer hydrochloride (SH; Renagelâ¢). Langmuir equilibrium binding affinities (K1) for LC and SH were established using different phosphorus (5-100 mM) and binder (134-670 mg per 50 mL) concentrations at pH 3-7, with or without salts of bile acids present (30 mM). At all pH levels, LC had a higher binding affinity for phosphate than SH. For LC, K1 was 6.1â±â1.0 mMâ1 and was independent of pH. For SH, K1 was pH dependent, being 1.5â±â0.8 mMâ1 at pH 5-7 and 0.025â±â0.002 mMâ1 at pH 3, that is, >200 times lower than for LC. In the presence of 30 mM 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 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2818-2827, 2007
Related Topics
Health Sciences
Pharmacology, Toxicology and Pharmaceutical Science
Drug Discovery
Authors
Valerie Autissier, Stephen J.P. Damment, Richard A. Henderson,