Matsuo Akira, Iida Akio, Tanimoto Minako, Matsushita Mutsuyoshi, Miyamoto Ken-ichi
Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute , Japan Tobacco Inc., Osaka , Japan and.
Ren Fail. 2014 Sep;36(8):1291-7. doi: 10.3109/0886022X.2014.930491. Epub 2014 Jun 30.
Hyperphosphatemia is a risk factor for arterial calcification contributing to the high-cardiovascular mortality in patients with chronic kidney disease (CKD). Ferric citrate hydrate (JTT-751) is being developed as a treatment for hyperphosphatemia with chronic renal failure and has shown a serum phosphorus-lowering effect in CKD patients. In this study, we evaluated the combination effect of JTT-751 with the phosphorus absorption-reducing effect of calcium carbonate and compared phosphorus absorption-reducing efficacy between three phosphate binders including JTT-751. Normal rats were fed a diet containing either 1% calcium carbonate, 1% JTT-751 or 1% JTT-751 with 1% calcium carbonate, for 7 days. Both 1% calcium carbonate and 1% JTT-751 alone reduced urinary phosphorus excretion, and the combined treatment reduced it more than each single-treatment, without clearly influencing calcium or iron-metabolism. Next, normal rats were fed a diet containing either 0.3, 1 and 3% lanthanum carbonate or 2.3% JTT-751, for 7 days. Either 3% lanthanum carbonate or 2.3% JTT-751 reduced urinary phosphorus excretion. Finally, we compared the reduced amount of urinary phosphorus excretion per dose of compound, of which JTT-751 is comparable to that of calcium carbonate and is greater than that of the lanthanum carbonate. In conclusion, JTT-751 showed an additive effect on the phosphorus absorption-reducing effect of calcium carbonate without influencing calcium- and iron-metabolism, and had a phosphorus absorption-reducing efficacy comparable to or greater than other existing phosphate binders.
高磷血症是动脉钙化的一个危险因素，会导致慢性肾脏病（CKD）患者心血管疾病死亡率升高。柠檬酸铁水合物（JTT-751）正被开发用于治疗慢性肾衰竭引起的高磷血症，并已在CKD患者中显示出降血清磷的效果。在本研究中，我们评估了JTT-751与碳酸钙降低磷吸收作用的联合效果，并比较了包括JTT-751在内的三种磷结合剂降低磷吸收的疗效。正常大鼠分别喂食含1%碳酸钙、1% JTT-751或1% JTT-751与1%碳酸钙的饲料7天。单独使用1%碳酸钙和1% JTT-751均可降低尿磷排泄，联合治疗降低尿磷排泄的效果比单一治疗更显著，且对钙或铁代谢无明显影响。接下来，正常大鼠分别喂食含0.3%、1%和3%碳酸镧或2.3% JTT-751的饲料7天。3%碳酸镧或2.3% JTT-751均可降低尿磷排泄。最后，我们比较了每剂量化合物降低尿磷排泄的量，其中JTT-751与碳酸钙相当，且大于碳酸镧。总之，JTT-751对碳酸钙降低磷吸收的作用具有相加效应，且不影响钙和铁代谢，其降低磷吸收的疗效与其他现有磷结合剂相当或更佳。
