Assessing Human Iron Kinetics Using Stable Iron Isotopic Techniques.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY Clinical Pharmacokinetics Pub Date : 2024-10-01 Epub Date: 2024-10-16 DOI:10.1007/s40262-024-01421-z
Nicole U Stoffel, Christophe Zeder, Michael B Zimmermann
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Abstract

Stable iron isotope techniques are critical for developing strategies to combat iron deficiency anemia, a leading cause of global disability. There are four primary stable iron isotope methods to assess ferrokinetics in humans. (i) The fecal recovery method applies the principles of a metabolic balance study but offers enhanced accuracy because the amount of iron isotope present in feces can be directly traced back to the labeled dose, distinguishing it from endogenous iron lost in stool from shed intestinal cells. (ii) In the plasma isotope appearance method, plasma samples are collected for several hours after oral dosing to evaluate the rate, quantity, and pattern of iron absorption. Key metrics include the time of peak isotope concentration and the area under the curve. (iii) The erythrocyte iron incorporation method measures iron bioavailability (absorption and erythrocyte iron utilization) from a whole blood sample collected 2 weeks after oral dosing. Simultaneous administration of oral and intravenous tracers allows for separate measurements of iron absorption and iron utilization. These three methods determine iron absorption by measuring tracer concentrations in feces, serum, or erythrocytes after administration of a tracer. In contrast, (iv) in iron isotope dilution, an innovative new approach, iron of natural composition acts as the tracer, diluting an ad hoc modified isotopic signature obtained via prior isotope administration and equilibration with body iron. This technique enables highly accurate long-term studies of iron absorption, loss, and gain. This review discusses the application of these kinetic methods and their potential to address important questions in hematology and iron biology.

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利用稳定铁同位素技术评估人体铁动力学。
稳定铁同位素技术对于制定防治缺铁性贫血的策略至关重要,缺铁性贫血是导致全球残疾的主要原因之一。有四种主要的稳定铁同位素方法可用于评估人体铁动力学。(i) 粪便回收法应用了代谢平衡研究的原理,但其准确性更高,因为粪便中的铁同位素含量可直接追溯到标记剂量,将其与脱落的肠细胞在粪便中损失的内源性铁区分开来。(ii) 在血浆同位素显现法中,口服药物后数小时收集血浆样本,以评估铁吸收的速度、数量和模式。关键指标包括同位素浓度达到峰值的时间和曲线下面积。(iii) 红细胞铁结合法是从口服给药两周后采集的全血样本中测定铁的生物利用度(吸收和红细胞铁利用)。同时口服和静脉注射示踪剂可分别测量铁的吸收和利用。这三种方法都是通过测量服用示踪剂后粪便、血清或红细胞中的示踪剂浓度来确定铁的吸收情况。相比之下,(iv) 铁同位素稀释法是一种创新的新方法,天然成分的铁充当示踪剂,稀释事先通过同位素给药并与体内铁平衡而获得的特别修正同位素特征。这种技术可对铁的吸收、流失和增加进行高度精确的长期研究。本综述将讨论这些动力学方法的应用及其解决血液学和铁生物学重要问题的潜力。
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来源期刊
CiteScore
8.80
自引率
4.40%
发文量
86
审稿时长
6-12 weeks
期刊介绍: Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
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