Pharmacology of the Phosphate Binder, Lanthanum Carbonate

• Published in: Renal failure Vol. 33; no. 2; pp. 217 - 224
• Main Author: Damment, Stephen J.P.
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.03.2011; Taylor & Francis
• Subjects: Aluminum Hydroxide - pharmacology; Aluminum Hydroxide - therapeutic use; Animals; Calcium - metabolism; Calcium Carbonate - pharmacology; Calcium Carbonate - therapeutic use; Chelating Agents - pharmacology; Chelating Agents - therapeutic use; chronic kidney disease; Dogs; Drug Evaluation, Preclinical; Feces - chemistry; hyperphosphatemia; Hyperphosphatemia - drug therapy; Hyperphosphatemia - etiology; kidney diseases; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - metabolism; Lanthanum - pharmacology; Lanthanum - therapeutic use; lanthanum carbonate; Lrnf Laboratory Study; Male; Mice; phosphate binder; Phosphates - analysis; Phosphates - pharmacokinetics; Phosphates - urine; Phosphorus Radioisotopes - analysis; Phosphorus Radioisotopes - urine; Polyamines - pharmacology; Polyamines - therapeutic use; Rats; Rats, Sprague-Dawley; Sevelamer
• ISSN: 0886-022X; 1525-6049
• DOI: 10.3109/0886022X.2011.552821

Studies were conducted to compare the phosphate-binding efficacy of lanthanum carbonate directly with other clinically used phosphate binders and to evaluate any potential adverse pharmacology. To examine the phosphate-binding efficacy, rats with normal renal function and chronic renal failure received lanthanum carbonate, aluminum hydroxide, calcium carbonate, or sevelamer hydrochloride in several experimental models. Lanthanum carbonate and aluminum hydroxide markedly increased excretion of [32P]-phosphate in feces and reduced excretion in urine in rats with normal renal function (p < 0.05), indicating good dietary phosphate-binding efficacy. In rats with chronic renal failure, lanthanum carbonate and aluminum hydroxide reduced urinary phosphate excretion to a greater degree and more rapidly than calcium carbonate, which in turn was more effective than sevelamer hydrochloride. The potential to induce adverse pharmacological effects was assessed systematically in mice, rats, and dogs with normal renal function using standard in vivo models. There was no evidence of any adverse secondary pharmacological effects of lanthanum carbonate on the central nervous, cardiovascular, respiratory, or gastrointestinal systems. These studies indicate that lanthanum carbonate is the more potent of the currently available dietary phosphate binders. No adverse secondary pharmacological actions were observed in vivo in a systematic evaluation at high doses.