Impact of Albumin Binding Function on Pharmacokinetics and Pharmacodynamics of Furosemide.
Impact of Albumin Binding Function on Pharmacokinetics and Pharmacodynamics of Furosemide.
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DOI：
10.3390/medicina58121780
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发表时间：
2022-12-02
期刊：
影响因子：
--
通讯作者：
Mitzner S
中科院分区：
文献类型：
--
作者：
Klinkmann G;Klammt S;Jäschke M;Henschel J;Gloger M;Reuter DA;Mitzner S
背景和目的：白蛋白与利尿尿环结合是其转运到肾脏和随后的小管分泌的基础，这是其治疗效果的先决条件。因此，白蛋白浓度越高，呋塞米的疗效越好。然而，关于呋塞米联合白蛋白的研究结果，以及呋塞米治疗低白蛋白血症的疗效，并没有证实这一假设。本研究的目的是确定呋塞米的疗效，不仅与白蛋白浓度有关，而且考虑到白蛋白的功能。材料与方法：在一项前瞻性、非介入性临床观察试验中，对50例接受持续静脉速尿治疗的重症监护患者的血液和尿液样本进行评估。白蛋白结合能力（ABiC）的测定可以通过定量荧光标记丹基肌氨酸的未结合部分，得出白蛋白结合位点特异性负载状态的结论。此外，采用高效液相色谱-质谱法测定血浆和尿液中呋塞米总浓度以及血浆中游离呋塞米组分的浓度。用尿排泄与液体摄入的比值来评价速尿的疗效。结果：与ABiC较低的患者相比，ABiC≥60%的患者尿中呋塞米游离分数显著降低（p < 0.001），尿中呋塞米浓度较高（p = 0.136），输注呋塞米肾脏排泄比例显著高于输注呋塞米（p = 0.010）。ABiC与开始速尿治疗后尿液排泄与液体输入比的增加呈正相关（r = 0.908, p = 0.017）。结论：ABiC可作为个体对呋塞米反应的标志物，并可用于制定患者特异性治疗方案。鉴于本研究的患者数量相对较少，未来应在更大规模的研究中研究呋塞米疗效与白蛋白功能之间的关系。
Background and Objectives: Albumin binding of the loop diuretic furosemide forms the basis for its transport to the kidney and subsequent tubular secretion, which is a prerequisite for its therapeutic effects. Accordingly, high albumin concentrations should result in higher efficacy of furosemide. However, study results on the combination of furosemide in conjunction with albumin, and on the efficacy of furosemide in hypoalbuminemia, did not confirm this hypothesis. The aim of this study was to determine the efficacy of furosemide not only in relation to albumin concentration, but also taking albumin function into account. Materials and Methods: In a prospective and non-interventional clinical observational trial, blood and urine samples from 50 intensive care patients receiving continuous intravenous furosemide therapy were evaluated. Albumin binding capacity (ABiC) determination allowed conclusions to be drawn about the binding site-specific loading state of albumin, by quantifying the unbound fraction of the fluorescent marker dansylsarcosine. In addition, assessment of the total concentration of furosemide in plasma and urine, as well as the concentration of free furosemide fraction in plasma, was performed by HPLC–MS. The efficacy of furosemide was evaluated by the ratio of urine excretion to fluid intake. Results: In patients with an ABiC ≥ 60% free furosemide fraction was significantly lower compared to patients with a lower ABiC (p < 0.001), urinary furosemide concentration was higher (p = 0.136), and a significantly higher proportion of infused furosemide was excreted renally (p = 0.010). ABiC was positively correlated (r = 0.908, p = 0.017) with increase in the urine excretion to fluid input ratio after initiation of furosemide therapy. Conclusions: ABiC could serve as a marker for individual response to furosemide and could be used to generate patient-specific therapeutic regimens. In view of the relatively low number of patients in this study, the relationship between furosemide efficacy and albumin function should be investigated in larger studies in the future.
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DOI：
10.1186/cc11454
发表时间：
2013-02-04
期刊：
Critical care (London, England)
影响因子：
--
作者：
Kellum JA;Lameire N;KDIGO AKI Guideline Work Group
通讯作者：
KDIGO AKI Guideline Work Group
影响因子：
13.6
作者：
Wilcox, CS
通讯作者：
Wilcox, CS
影响因子：
3.3
作者：
Zaidi, Nida;Ahmad, Ejaz;Khan, Rizwan H.
通讯作者：
Khan, Rizwan H.
DOI：
10.1053/j.ajkd.2016.08.027
发表时间：
2017-01
期刊：
American journal of kidney diseases : the official journal of the National Kidney Foundation
影响因子：
--
作者：
Hoorn EJ;Ellison DH
通讯作者：
Ellison DH
影响因子：
19.6
作者：
INOUE, M;OKAJIMA, K;MORINO, Y
通讯作者：
MORINO, Y