幼儿意外中毒:维拉唑酮及其尿代谢物M17与滥用药物筛选免疫测定缺乏交叉反应性

Q2 Medicine
BMC Clinical Pathology Pub Date : 2019-02-18 eCollection Date: 2019-01-01 DOI:10.1186/s12907-019-0084-9
Christina D Martinez-Brokaw, Joshua B Radke, Joshua G Pierce, Alexandra Ehlers, Sean Ekins, Kelly E Wood, Jon Maakestad, Jacqueline A Rymer, Kenichi Tamama, Matthew D Krasowski
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引用次数: 2

摘要

背景:维拉唑酮是FDA批准用于治疗重度抑郁症的药物。作者描述了两例意外接触维拉唑酮的幼儿,他们表现出与安非他明接触相似的症状,也出现了无法解释的安非他明尿液免疫测定药物筛查阳性。鉴于缺乏关于维拉唑酮及其代谢物与滥用药物筛选试验交叉反应性的公开数据,作者使用计算和经验方法研究了维拉唑酮及其代谢物的滥用药物免疫测定交叉反应性。方法:为了确定维拉唑酮与药物滥用筛选免疫测定交叉反应的可能性,作者评估了维拉唑酮亲本分子和已知代谢物与尿液免疫测定药物筛选抗原靶点阵列的二维相似性。为了便于对市售的M17代谢物进行研究,采用一种新的合成方案制备了M17。将维拉唑酮和M17加入尿液(200-100,000 ng/mL)和血清(20-2000 ng/mL)中,检测尿液和血清的交叉反应性。结果:二维相似度计算分析显示,维拉唑酮及其代谢物与常用滥用药物筛选免疫测定的抗原靶点相似度普遍较低,预测交叉反应性弱或无交叉反应性。M17代谢物与安非他明和三环抗抑郁药具有2D相似性,在这些免疫测定中与其他一些具有弱交叉反应性的化合物相似。因此,对两种不同的尿安非他明免疫测定和血清三环抗抑郁药免疫测定进行了交叉反应性试验。然而,维拉唑酮和M17代谢物的交叉反应性的实际测试没有检测到任何尿安非他明筛选浓度高达100,000 ng/mL和血清三环抗抑郁药测定浓度高达2000 ng/mL的交叉反应性。结论:虽然维拉唑酮代谢物M17与安非他命和三环抗抑郁药具有较弱的2D结构相似性,但目前的研究并未证明与两种不同的尿安非他命免疫测定和血清三环抗抑郁药免疫测定有任何实验交叉反应性。幼儿服用维拉唑酮与服用安非他明相似,且缺乏对维拉唑酮的常规实验室检测,这给诊断带来了挑战。需要进一步的工作来了解维拉唑酮在儿童和成人中的代谢特征。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Accidental intoxications in toddlers: lack of cross-reactivity of vilazodone and its urinary metabolite M17 with drug of abuse screening immunoassays.

Accidental intoxications in toddlers: lack of cross-reactivity of vilazodone and its urinary metabolite M17 with drug of abuse screening immunoassays.

Accidental intoxications in toddlers: lack of cross-reactivity of vilazodone and its urinary metabolite M17 with drug of abuse screening immunoassays.

Background: Vilazodone is an FDA approved medication used to treat major depressive disorder. The authors describe two cases of accidental vilazodone exposure in toddlers who presented with symptoms similar to amphetamine exposure and also with unexplained positive amphetamine urine immunoassay drug screens. Given a lack of published data on cross-reactivity of vilazodone and its metabolites with drug of abuse screening tests, the authors investigated drug of abuse immunoassay cross-reactivity of vilazodone and metabolites using computational and empirical approaches.

Methods: To ascertain the likelihood that vilazodone would cross-react with drug of abuse screening immunoassays, the authors assessed the two-dimensional (2D) similarity of the vilazodone parent molecule and known metabolites to an array of antigenic targets for urine immunoassay drug screens. To facilitate studies of the commercially unavailable M17 metabolite, it was prepared synthetically through a novel scheme. Urine and serum were spiked with vilazodone and M17 into urine (200-100,000 ng/mL) and serum (20-2000 ng/mL) samples and tested for cross-reactivity.

Results: Computational analysis using 2D similarity showed that vilazodone and metabolites have generally low similarity to antigenic targets of common drug of abuse screening immunoassays, predicting weak or no cross-reactivity. The M17 metabolite had 2D similarity to amphetamines and tricyclic antidepressants in a range similar to some other compounds exhibiting weak cross-reactivity on these immunoassays. Cross-reactivity testing was therefore performed on two different urine amphetamines immunoassays and a serum tricyclic antidepressant immunoassay. However, actual testing of cross reactivity for vilazodone and the M17 metabolite did not detect cross-reactivity for any urine amphetamines screen at concentrations up to 100,000 ng/mL and for a serum tricyclic antidepressants assays at concentrations up to 2000 ng/mL.

Conclusion: While the vilazodone metabolite M17 has weak 2D structural similarity to amphetamines and tricyclic antidepressants, the current study did not demonstrate any experimental cross-reactivity with two different urine amphetamines immunoassays and a serum tricyclic antidepressant immunoassay. Vilazodone ingestions in young children present a diagnostic challenge in their similarity to amphetamine ingestions and the lack of routine laboratory tests for vilazodone. Further work is needed to understand the metabolic profile for vilazodone in children versus adults.

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来源期刊
BMC Clinical Pathology
BMC Clinical Pathology Medicine-Pathology and Forensic Medicine
CiteScore
3.30
自引率
0.00%
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0
期刊介绍: BMC Clinical Pathology is an open access journal publishing original peer-reviewed research articles in all aspects of histopathology, haematology, clinical biochemistry, and medical microbiology (including virology, parasitology, and infection control). BMC Clinical Pathology (ISSN 1472-6890) is indexed/tracked/covered by PubMed, CAS, EMBASE, Scopus and Google Scholar.
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