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Reductions in plasma and urine mercury concentrations following N,N′bis-(2-mercaptoethyl) isophthalamide (NBMI) therapy: a post hoc analysis of data from a randomized human clinical trial
Biometals ( IF 3.5 ) Pub Date : 2023-11-21 , DOI: 10.1007/s10534-023-00560-3
David A Geier 1 , Mark R Geier 1
Affiliation  

Environmental mercury exposure possesses a significant risk to many human populations. At present there are no effective treatments for acute mercury toxicity. A new compound, N,N′bis-(2-mercaptoethyl) isophthalamide (NBMI), a lipophilic chelating agent was created to tightly/irreversibly bind mercury. A post hoc dose-dependent analysis of NBMI therapy was undertaken on data from a randomized controlled NBMI human treatment trial on 36 Ecuadorian gold miners with elevated urinary mercury concentrations. Study subjects were randomly assigned to receive 100 milligram (mg) NBMI/day, 300 mg NBMI/day, or placebo for 14 days. For each study subject daily mg NBMI dose/Kilogram (Kg) bodyweight were determined and plasma and urine mercury concentrations (micrograms (µg)/Liter (L)) on study day 1 (pre-NBMI treatment), 15 (after 14 days of NBMI treatment) and 45 (30 days after NBMI treatment) were correlated with NBMI dosing using the linear regression statistic in SAS. Regression revealed significant inverse correlations between increasing per mg NBMI/Kg bodyweight/day and reduced concentrations of urinary and plasma mercury on study day 15 (reduced by in urine = 18–20 µg/L and plasma = 2 µg/L) and study day 30 (reduced by in urine = 15–20 µg/L and plasma = 4 µg/L) and significant correlations between reductions in mercury concentrations in urine and plasma. Significant 30% reductions in urinary mercury concentrations per mg NBMI/Kg bodyweight/day administered for 14 days were observed. This study supports the dose-dependent ability of NBMI therapy to significantly reduce mercury concentrations, particularly in the urine, in an acutely mercury exposed human population. NBMI therapy should be evaluated in other mercury exposed populations.



中文翻译:

N,N′双(2-巯基乙基)间苯二甲酰胺 (NBMI) 治疗后血浆和尿液汞浓度的降低:对随机人体临床试验数据的事后分析

环境汞暴露对许多人群构成重大风险。目前还没有针对急性汞中毒的有效治疗方法。一种新化合物 N,N' 双(2-巯基乙基)间苯二甲酰胺 (NBMI) 是一种亲脂性螯合剂,可紧密/不可逆地结合汞。对 36 名尿汞浓度升高的厄瓜多尔金矿工人进行的随机对照 NBMI 人体治疗试验的数据进行了 NBMI 治疗的事后剂量依赖性分析。研究受试者被随机分配接受 100 毫克 (mg) NBMI/天、300 毫克 NBMI/天或安慰剂,为期 14 天。对于每个研究对象,每天测定毫克 NBMI 剂量/千克 (Kg) 体重,并在研究第 1 天(NBMI 治疗前)、第 15 天(治疗 14 天后)测定血浆和尿液汞浓度(微克 (μg)/升 (L))。 NBMI 治疗)和 45(NBMI 治疗后 30 天)使用 SAS 中的线性回归统计与 NBMI 剂量相关。回归显示,在研究第 15 天(尿液中减少 = 18–20 µg/L,血浆 = 2 µg/L)和研究日,每毫克 NBMI/公斤体重/天的增加与尿液和血浆汞浓度的降低之间存在显着的负相关30(尿液中汞浓度降低 = 15–20 µg/L,血浆汞浓度 = 4 µg/L),并且尿液和血浆中汞浓度降低之间存在显着相关性。连续 14 天,每天每毫克 NBMI/公斤体重给药,尿汞浓度显着降低 30%。这项研究支持 NBMI 疗法具有剂量依赖性能力,可以显着降低严重汞暴露人群中的汞浓度,特别是尿液中的汞浓度。NBMI 治疗应在其他汞暴露人群中进行评估。

更新日期:2023-11-23
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