Shire Pharmaceuticals, Hampshire International Business Park, Chineham, Basingstoke, UK.
Ren Fail. 2011;33(2):217-24. 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 [(32)P]-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.
研究旨在比较碳酸镧与其他临床应用的磷结合剂的磷结合效果，并评估任何潜在的不良药理学作用。为了考察磷结合效果，在几种实验模型中，给肾功能正常和慢性肾衰竭的大鼠分别给予碳酸镧、氢氧化铝、碳酸钙或盐酸司维拉姆。碳酸镧和氢氧化铝可明显增加肾功能正常大鼠粪便中 [(32)P]-磷酸盐的排泄量，并减少尿液中的排泄量（p < 0.05），表明具有良好的饮食磷结合效果。在慢性肾衰竭大鼠中，碳酸镧和氢氧化铝比碳酸钙更能快速地减少尿磷排泄，而碳酸钙比盐酸司维拉姆更有效。在肾功能正常的小鼠、大鼠和狗中，使用标准的体内模型系统地评估了潜在的不良药理作用。没有证据表明碳酸镧对中枢神经系统、心血管系统、呼吸系统或胃肠道系统有任何不良的继发药理作用。这些研究表明，碳酸镧是目前可用的饮食磷结合剂中更有效的一种。在高剂量的系统评价中，体内未观察到任何不良的继发药理作用。
