基于生理机理的静脉注射铁的全身药代动力学模型。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Drug Delivery and Translational Research Pub Date : 2025-04-01 Epub Date: 2024-07-24 DOI:10.1007/s13346-024-01675-x
Xiaoqing Fan, Kangna Cao, Raymond S M Wong, Xiaoyu Yan
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引用次数: 0

摘要

铁是哺乳动物机体每个细胞所必需的。缺铁是世界范围内的一个主要公共卫生问题。静脉注射铁剂一直被用于治疗贫血。然而,静脉注射铁剂疗法远未达到理想状态,因为在不同的铁状态下,静脉注射铁剂的药代动力学和生物分布之间的定量关系仍不清楚。众所周知,患者会因过量的铁积累而受到不良影响。我们的目标是在小鼠体内建立一个基于生理学的铁药代动力学(PBPK)模型,并验证其在预测大鼠和人体铁分布中的应用。为了构建小鼠体内铁的 PBPK 模型,我们收集了以前发表的有关铁的数据,然后根据与每个物种相关的特定生理和化学参数将其推断到大鼠和人体内。PBPK 模型成功地描述了铁在小鼠体内的分布特征。基于大鼠外推的模型准确地模拟了大鼠组织中羧甲基麦芽糖铁(FCM)的 PK 曲线。同样,观察到的和模拟的人体血清中羧甲基铁的 PK 值也基本吻合。这种机理性全身 PBPK 模型有助于理解和预测铁对不同物种的影响。它还为今后结合铁动力学和生物分布以及相关临床实验的研究奠定了基础。这种方法可以开发出有效的个性化缺铁性贫血治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A whole-body mechanistic physiologically-based pharmacokinetic modeling of intravenous iron.

A whole-body mechanistic physiologically-based pharmacokinetic modeling of intravenous iron.

Iron is essential for every cell of the mammalian organism. Iron deficiency is a major public health issue worldwide. Intravenous (IV) iron therapy has been used to treat anemia. However, IV iron therapy is known far away from ideal because the quantitative relationship between the pharmacokinetics and biodistribution of IV iron under different iron statuses remains unclear. Patients are known to suffer adverse effects from excessive iron accumulation. Our objective was to develop a physiologically based pharmacokinetic (PBPK) model of iron in mice and validate its application for predicting iron disposition in rats and humans. Previously published data on iron were collected for constructing the PBPK model of iron in mice, and then extrapolated to rats and humans based on physiologically and chemically specific parameters relevant to each species. The PBPK model characterized the distribution of iron in mice successfully. The model based on extrapolation to rats accurately simulated the ferric carboxymaltose (FCM) PK profiles in rat tissues. Similarly, the observed and simulated serum PK of FCM in humans were in reasonable agreement. This mechanistic whole-body PBPK model is useful for understanding and predicting iron effects on different species. It also establishes a foundation for future research that incorporates iron kinetics and biodistribution, along with related clinical experiments. This approach could lead to the development of effective and personalized iron deficiency anemia treatments.

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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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