Transferrin saturation with intravenous irons: An in vitro study
Transferrin saturation with intravenous irons: An in vitro study
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DOI：
10.1111/j.1523-1755.2004.00864.x
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发表时间：
2004-09-01
影响因子：
19.6
通讯作者：
Agarwal, R
中科院分区：
文献类型：
--
作者：
Agarwal, R
背景资料。慢性肾脏疾病的缺铁性贫血通常用三种静脉注射铁中的一种--葡聚糖铁、蔗糖铁或葡萄糖酸铁。不同药物之间存在着实质性的药理差异，但它们饱和转铁蛋白的能力尚未进行比较。如果转移介导的铁摄取是这种毒性的基础，可能导致转铁蛋白快速饱和的药物可能会导致更好的疗效，但也会增加毒性。我们研究了三种静脉注射铁给转铁蛋白的体外能力。通过尿素聚丙烯酰胺凝胶电泳法(PAGE)直接显示转铁蛋白条带，以及以剂量依赖(0~100µg/mL)和时间依赖(15~180分钟)的方式评价铁对半饱和转铁蛋白的能力，来研究转铁蛋白的饱和度。计算饱和转铁蛋白所需铁的半最大剂量(EC50)。非葡聚糖铁能够以剂量依赖和时间依赖的方式饱和转铁蛋白。与蔗糖铁相比，葡萄糖酸铁的转铁蛋白饱和速度更快。蔗糖铁的EC50值与剂量葡萄糖酸铁滴定曲线的斜率分别为-0.021、0.006和0.001，95%CI分别为-0.006和0.001。计算平均铁浓度的最小二乘平均EC50：葡萄糖酸铁为5.95nmol(95%CI为5.82~6.08)，蔗糖铁为6.73nmol(95%CI为6.59~6.86)，葡聚糖铁为7.24nmol(95%CI为7.11~7.38)。依赖时间的转铁蛋白饱和度也有类似的结果(药物x时间相互作用，F6.0，P<；0.01)。尿素PAGE分析结果与功能分析结果相似。铁药物在体外直接铁转移的显著异质性表明，这些药物在体内的安全性和有效性可能存在差异。需要进行体内研究来比较现有非葡聚糖肠外熨斗的安全性和有效性，以更好地确定治疗比率。
Background. Iron deficiency anemia in chronic kidney disease is commonly treated with one of three intravenous irons-iron dextran, iron sucrose, or iron gluconate. Substantial pharmacologic differences between drugs exist, but their ability to saturate transferrin has not been compared. Drugs that may lead to rapid transferrin saturation may lead to greater efficacy but also increased toxicity if transferring-mediated uptake of iron is the basis of this toxicity.Methods. We studied the in vitro ability of the three intravenous irons to donate iron to transferrin. Transferrin saturation was studied by direct visualization of the transferrin bands by urea polyacrylamide gel electrophoresis (PAGE), as well as a functional assay that evaluated the ability of iron to half saturate transferrin in a dose-dependent (0 to 100 mug/mL) and time-dependent (15 to 180 min) manner. Half-maximal dose (EC50) of iron needed to saturate transferrin was evaluated.Results. Nondextran irons were able to saturate transferrin in a dose-dependent and time-dependent manner. There was more rapid transferrin saturation with iron gluconate compared to iron sucrose. The slope of the EC50 versus dose iron gluconate titration curve was -0.021 nmol/mug/mL (95% CI -0.025 to -0.017, P < 0.0001), for iron sucrose -0.006 nmol/mug/mL (95% CI -0.010 to -0.002, P= 0.002), and for iron dextran -0.001 nmol/mug/mL (95% CI -0.004 to 0.003, P > 0.2). The least square mean EC50 computed for mean iron concentration was 5.95 nmol for iron gluconate (95% CI 5.82 to 6.08), 6.73 nmol for iron sucrose (95% CI 6.59 to 6.86), and 7.24 nmol for iron dextran (95% CI 7.11 to 7.38). Similar results were seen for the time-dependent transferrin saturation (drug x time interaction, F 6.0, P < 0.01). Urea PAGE analysis showed similar results as the functional assay.Conclusion. Substantial heterogeneity in direct iron transfer from iron pharmaceuticals in vitro suggests that differences may exist in safety and efficacy of these drugs in vivo. In vivo studies are needed to compare the safety and efficacy of existing nondextran parenteral irons to better define the therapeutic ratio.