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铁基磷酸盐结合剂PA21在体外生理pH范围内具有强大的磷酸盐结合能力且铁释放量极少。

The iron-based phosphate binder PA21 has potent phosphate binding capacity and minimal iron release across a physiological pH range in vitro.

作者信息

Wilhelm Maria, Gaillard Sylvain, Rakov Viatcheslav, Funk Felix

机构信息

Vifor (International) Inc., St. Gallen, and Vifor Pharma, Glattbrugg, Switzerland.

出版信息

Clin Nephrol. 2014 Apr;81(4):251-8. doi: 10.5414/cn108119.

Abstract

AIMS

Hyperphosphatemia in advanced chronic kidney disease (CKD) necessitates the use of phosphate binders. This in vitro study assessed phosphate binding and Fe release properties of the novel iron-based phosphate binder PA21.

MATERIALS AND METHODS

Phosphate adsorption and Fe release were assessed under conditions simulating administration of PA21 on an empty stomach and full stomach across a pH range to which PA21 would be exposed during passage through the gastrointestinal (GI) tract.

RESULTS

PA21 showed a robust phosphate binding capacity over the entire physiologically relevant pH range. The high binding capacity at low pH indicates that phosphate binding could begin in the stomach. Under the current experimental setting, the maximal bound phosphate to Fe ratio was 0.47 mmol P/mmol Fe. The largest amount of Fe release was observed at the lowest pH without phosphate and was much lower in the presence of phosphate. These results are in line with the formation of iron phosphate at low pH, as indicated by X-ray photoelectron spectroscopy and thermodynamic calculations. Fe release was minimal (≤ 0.35%) across pH 2.5 - 8.5.

CONCLUSIONS

These studies demonstrate that PA21 has potent phosphate binding capacity and low iron release over a physiologically relevant pH range in the GI tract. These features indicate PA21 could be an effective alternative phosphate binder for CKD patients.

摘要

目的

晚期慢性肾脏病(CKD)患者出现高磷血症时需要使用磷结合剂。本体外研究评估了新型铁基磷结合剂PA21的磷结合和铁释放特性。

材料与方法

在模拟PA21空腹和饱腹给药的条件下,在PA21通过胃肠道(GI)时可能暴露的pH范围内,评估磷吸附和铁释放情况。

结果

PA21在整个生理相关pH范围内均显示出强大的磷结合能力。低pH下的高结合能力表明磷结合可在胃中开始。在当前实验设置下,最大结合磷与铁的比率为0.47 mmol P/mmol Fe。在无磷的最低pH下观察到最大量的铁释放,而在有磷存在时铁释放量低得多。如X射线光电子能谱和热力学计算所示,这些结果与低pH下形成磷酸铁一致。在pH 2.5 - 8.5范围内铁释放量极小(≤ 0.35%)。

结论

这些研究表明,PA21在胃肠道生理相关pH范围内具有强大的磷结合能力和低铁释放特性。这些特性表明PA21可能是CKD患者有效的替代磷结合剂。

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