Comparison of Dietary Phosphate Absorption After Single Doses of Lanthanum Carbonate and Sevelamer Carbonate in Healthy Volunteers: A Balance Study

被引:34
作者
Martin, Patrick [1 ]
Wang, Phillip [1 ]
Robinson, Antoine [1 ]
Poole, Lynne [2 ]
Dragone, Jeffrey [1 ]
Smyth, Michael [2 ]
Pratt, Raymond [1 ]
机构
[1] Shire Pharmaceut, Wayne, PA 19087 USA
[2] Shire Pharmaceut, Basingstoke, Hants, England
关键词
Chronic kidney disease; clinical trial; lanthanum carbonate; phosphate binder; sevelamer carbonate; CORONARY-ARTERY CALCIFICATION; HEMODIALYSIS-PATIENTS; CALCIUM-CARBONATE; IN-VITRO; PHOSPHORUS; MORTALITY; BINDERS; HYPERPHOSPHATEMIA; PROGRESSION; METABOLISM;
D O I
10.1053/j.ajkd.2010.11.028
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:700 / 706
页数:7
相关论文
共 32 条
  • [1] Relative in vitro efficacy of the phosphate binders lanthanum carbonate and sevelamer hydrochloride
    Autissier, Valerie
    Damment, Stephen J. P.
    Henderson, Richard A.
    [J]. JOURNAL OF PHARMACEUTICAL SCIENCES, 2007, 96 (10) : 2818 - 2827
  • [2] Mineral metabolism, mortality, and morbidity in maintenance hemodialysis
    Block, GA
    Klassen, PS
    Lazarus, JM
    Ofsthun, N
    Lowrie, EG
    Chertow, GM
    [J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2004, 15 (08): : 2208 - 2218
  • [3] Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis
    Block, GA
    Spiegel, DM
    Ehrlich, J
    Mehta, R
    Lindbergh, J
    Dreisbach, A
    Raggi, P
    [J]. KIDNEY INTERNATIONAL, 2005, 68 (04) : 1815 - 1824
  • [4] RenaGel(R), a novel calcium- and aluminium-free phosphate binder, inhibits phosphate absorption in normal volunteers
    Burke, SK
    Slatopolsky, EA
    Goldberg, DI
    [J]. NEPHROLOGY DIALYSIS TRANSPLANTATION, 1997, 12 (08) : 1640 - 1644
  • [5] Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients
    Chertow, GM
    Burke, SK
    Raggi, P
    [J]. KIDNEY INTERNATIONAL, 2002, 62 (01) : 245 - 252
  • [6] Consistent control of mineral and bone disorder in incident hemodialysis patients
    Danese, Mark D.
    Belozeroff, Vasily
    Smirnakis, Karen
    Rothman, Kenneth J.
    [J]. CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2008, 3 (05): : 1423 - 1429
  • [7] DAVIS GR, 1983, GASTROENTEROLOGY, V85, P908
  • [8] DAVIS GR, 1980, GASTROENTEROLOGY, V78, P991
  • [9] Delmez J, 2007, CLIN NEPHROL, V68, P386
  • [10] *DIAL OUTC PRACT P, 2009 ANN REP DIAL OU