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健康大鼠及贫血、铁过载或炎症模型中铁动力学研究:蔗糖铁氧羟化物或柠檬酸铁治疗后的变化。

Iron kinetics following treatment with sucroferric oxyhydroxide or ferric citrate in healthy rats and models of anaemia, iron overload or inflammation.

机构信息

Division of Nephrology, RWTH University Hospital Aachen, Germany.

Department of Medical Affairs, Vifor Pharma, Glattbrugg, Switzerland.

出版信息

Nephrol Dial Transplant. 2020 Jun 1;35(6):946-954. doi: 10.1093/ndt/gfaa030.

Abstract

BACKGROUND

The iron-based phosphate binders, sucroferric oxyhydroxide (SFOH) and ferric citrate (FC), effectively lower serum phosphorus in clinical studies, but gastrointestinal iron absorption from these agents appears to differ. We compared iron uptake and tissue accumulation during treatment with SFOH or FC using experimental rat models.

METHODS

Iron uptake was evaluated during an 8-h period following oral administration of SFOH, FC, ferrous sulphate (oral iron supplement) or control (methylcellulose vehicle) in rat models of anaemia, iron overload and inflammation. A 13-week study evaluated the effects of SFOH and FC on iron accumulation in different organs.

RESULTS

In the pharmacokinetic experiments, there was a minimal increase in serum iron with SFOH versus control during the 8-h post-treatment period in the iron overload and inflammation rat models, whereas a moderate increase was observed in the anaemia model. Significantly greater increases (P < 0.05) in serum iron were observed with FC versus SFOH in the rat models of anaemia and inflammation. In the 13-week iron accumulation study, total liver iron content was significantly higher in rats receiving FC versus SFOH (P < 0.01), whereas liver iron content did not differ between rats in the SFOH and control groups.

CONCLUSIONS

Iron uptake was higher from FC versus SFOH following a single dose in anaemia, iron overload and inflammation rat models and 13 weeks of treatment in normal rats. These observations likely relate to different physicochemical properties of SFOH and FC and suggest distinct mechanisms of iron absorption from these two phosphate binders.

摘要

背景

铁基磷酸盐结合剂,蔗糖铁氧羟化物(SFOH)和柠檬酸铁(FC),在临床研究中有效地降低血清磷,但这些药物的胃肠道铁吸收似乎不同。我们使用实验大鼠模型比较了 SFOH 或 FC 治疗期间的铁摄取和组织积累。

方法

在贫血、铁过载和炎症大鼠模型中,在口服 SFOH、FC、硫酸亚铁(口服铁补充剂)或对照(甲基纤维素载体)后的 8 小时期间评估铁摄取。一项为期 13 周的研究评估了 SFOH 和 FC 对不同器官中铁积累的影响。

结果

在药代动力学实验中,与对照相比,SFOH 在铁过载和炎症大鼠模型中在治疗后 8 小时内血清铁仅略有增加,而在贫血模型中观察到中度增加。与 SFOH 相比,FC 在贫血和炎症大鼠模型中观察到血清铁显著增加(P<0.05)。在 13 周的铁积累研究中,与 SFOH 相比,FC 组大鼠的总肝铁含量显著升高(P<0.01),而 SFOH 组和对照组大鼠的肝铁含量无差异。

结论

在贫血、铁过载和炎症大鼠模型中,单次剂量后从 FC 摄取的铁比 SFOH 更高,在正常大鼠中 13 周的治疗后也是如此。这些观察结果可能与 SFOH 和 FC 的不同物理化学性质有关,并表明这两种磷酸盐结合剂的铁吸收具有不同的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f3b/7282824/2a275c5a5c47/gfaa030f1.jpg

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