Background: Lanthanum carbonate and sevelamer carbonate are noncalcium phosphate binders used to treat hyperphosphatemia in patients with chronic kidney disease. This is the first study to compare phosphate absorption from a standardized meal ingested with a typical clinical dose of these binders. Study Design: Randomized open-label crossover study. Settings & Participants: Healthy volunteers were confined to a clinical research center during 4 study periods. Of 31 volunteers randomly assigned, 19 completed all treatments and 18 were analyzed in the pharmacodynamic set (1 was excluded because of vomiting). Intervention: Participants were assigned in random order to meal alone, meal plus lanthanum carbonate (1 tablet containing 1,000 mg of elemental lanthanum), and meal plus sevelamer carbonate (three 800-mg tablets). The gastrointestinal tract was cleared, the meal was ingested (+/- treatment), and rectal effluent was collected. In a fourth period, volunteers repeated the study procedures while fasting. Outcomes: The primary end point, net phosphate absorption, was analyzed using a mixed-effect linear model. Measurements: Phosphorus content of effluent and duplicate meal samples were measured using inductively coupled plasma-optical emission spectroscopy. Results: The standard meal contained similar to 375 mg of phosphate, 75% of which was absorbed (net absorption, 281.7 +/- 14.1 mg [adjusted mean +/- standard error]). Lanthanum carbonate decreased net phosphate absorption by 45% (net absorption, 156.0 +/- 14.2 mg) compared with 21% (net absorption, 221.8 +/- 14.1 mg) for sevelamer carbonate (P < 0.001). Lanthanum carbonate bound 135.1 +/- 12.3 mg of phosphate, whereas sevelamer carbonate bound 63.2 +/- 12.3 mg, a 71.9-mg difference (95% CI, 40.0-103.8; P < 0.001). Per tablet, this equates to 135 mg of phosphate bound with lanthanum carbonate versus 21 mg with sevelamer carbonate. Limitations: A single-dose study. Conclusions: In healthy volunteers, 1,000 mg of lanthanum carbonate decreased phosphate absorption by 45% compared with a 21% decrease with 2,400 mg of sevelamer carbonate. Am J Kidney Dis. 57(5): 700-706. (C) 2011 by the National Kidney Foundation, Inc.