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

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 hydr...

Full description

Saved in:
Bibliographic Details
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
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.20956