Ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and 2 clinical trials.
Ethyl glucuronide and ethyl sulfate assays in clinical trials, interpretation, and limitations: results of a dose ranging alcohol challenge study and 2 clinical trials.
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DOI：
10.1111/acer.12407
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发表时间：
2014-07
期刊：
影响因子：
--
通讯作者：
O'Malley SS
中科院分区：
文献类型：
--
作者：
Jatlow PI;Agro A;Wu R;Nadim H;Toll BA;Ralevski E;Nogueira C;Shi J;Dziura JD;Petrakis IL;O'Malley SS
乙醇代谢物乙基葡萄糖醛酸 (EtG) 和硫酸乙酯 (EtS) 是近期饮酒的生物标志物，可提供客观的戒酒衡量标准。我们的目标是更好地了解截止浓度对测试解释的影响、测量两种代谢物的必要性，以及如何最好地将测试结果与临床试验中的自我报告结合起来。受试者 (n=18) 每隔一周服用 3 杯酒精剂量，校准后的血液浓度分别为 20、80 和 120 mg/dL。在 24 小时住院期间定期测量尿液 EtG/EtS，此后每天测量两次。此外，2 项临床试验的参与者还提供了 EtG/EtS 和饮酒史样本。评估了 100/50、200/100 和 500/250 ng/mL 的 EtG/EtS 临界值。每次攻击后 12 小时，EtG 在 100 和 200 截止值处始终呈阳性，但在 24 小时时，低剂量后所有截止值的敏感性都很差，48 小时后，无论剂量或截止值如何，敏感性都很差。同样，在临床试验中，EtG 灵敏度对于检测过去 24 小时内两个最低截止值的饮酒情况很有帮助，但在过去 24-48 小时内低于 40%。灵敏度在 500 ng/mL 截止值处降低。 EtG 和 EtS 之间的差异很少。自我戒酒报告与 EtG 确认的戒酒情况的比较表明饮酒情况漏报。前一天晚上饮酒的情况应在第二天早上即可检测到，EtG 临界值为 100 或 200 ng/mL。饮酒后二十四小时，轻度饮酒的敏感性较差，但对于大量饮酒的敏感性良好。 48 小时内，饮酒 6 杯或更少后，敏感性较低。将截止值增加到 500 ng/mL 会导致灵敏度大幅降低。通常不需要同时监测 EtG 和 EtS。我们建议 EtG 确认自我戒断报告，以评估临床试验的结果。
The ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS) are biomarkers of recent alcohol consumption that provide objective measures of abstinence. Our goals are to better understand the impact of cutoff concentration on test interpretation, the need for measuring both metabolites, and how best to integrate test results with self-reports in clinical trials. Subjects (n=18) were administered, one week apart, 3 alcohol doses calibrated to achieve blood concentrations of 20, 80 and 120 mg/dL respectively. Urinary EtG/EtS were measured at timed intervals during a 24 hour hospitalization and twice daily thereafter. In addition, participants from 2 clinical trials provided samples for EtG/EtS and drinking histories. Cutoffs for EtG/EtS of 100/50, 200/100 and 500/250 ng/mL were evaluated. Twelve hours following each challenge, EtG was always positive at the 100 and 200 cutoffs, but at 24 hours sensitivity was poor at all cutoffs following the low dose, and poor after 48 hours regardless of dose or cutoff. Similarly, in the clinical trials EtG sensitivity was good for detecting any drinking during the last 24 hours at the two lowest cutoffs, but under 40% during the last 24-48 hours. Sensitivity was reduced at the 500 ng/mL cutoff. Discrepancies between EtG and EtS were few. Comparison of self- reports of abstinence and EtG confirmed abstinence indicated under-reporting of drinking. Any drinking the night before should be detectable the following morning with EtG cutoffs of 100 or 200 ng/mL. Twenty-four hours after drinking, sensitivity is poor for light drinking, but good for heavier consumption. At 48 hours, sensitivity is low following 6 drinks or less. Increasing the cutoff to 500 ng/mL leads to substantially reduced sensitivity. Monitoring both EtG and EtS should usually be unnecessary. We recommend EtG confirmed self-reports of abstinence for evaluation of outcomes in clinical trials.
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