Martinez-Brokaw Christina D, Radke Joshua B, Pierce Joshua G, Ehlers Alexandra, Ekins Sean, Wood Kelly E, Maakestad Jon, Rymer Jacqueline A, Tamama Kenichi, Krasowski Matthew D
1Department of Chemistry, College of Sciences, NC State University, Raleigh, NC 27695 USA.
2Comparative Medicine Institute, NC State University, Raleigh, NC 27695 USA.
BMC Clin Pathol. 2019 Feb 18;19:2. doi: 10.1186/s12907-019-0084-9. eCollection 2019.
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.
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.
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.
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.
维拉唑酮是一种经美国食品药品监督管理局（FDA）批准用于治疗重度抑郁症的药物。作者描述了两例幼儿意外接触维拉唑酮的病例，这些幼儿出现了与苯丙胺接触相似的症状，且尿液苯丙胺免疫分析药物筛查结果呈阳性但原因不明。鉴于缺乏关于维拉唑酮及其代谢物与药物滥用筛查试验交叉反应性的已发表数据，作者采用计算和实证方法研究了维拉唑酮及其代谢物与药物滥用免疫分析的交叉反应性。
为确定维拉唑酮与药物滥用筛查免疫分析发生交叉反应的可能性，作者评估了维拉唑酮母体分子和已知代谢物与一系列尿液免疫分析药物筛查抗原靶点的二维（2D）相似性。为便于对无法通过商业途径获得的M17代谢物进行研究，通过一种新方案对其进行了合成制备。将维拉唑酮和M17加入尿液（200 - 100,000 ng/mL）和血清（20 - 2000 ng/mL）样本中，然后检测交叉反应性。
使用二维相似性进行的计算分析表明，维拉唑酮及其代谢物与常见药物滥用筛查免疫分析的抗原靶点总体相似性较低，预测交叉反应性较弱或无交叉反应。M17代谢物与苯丙胺和三环类抗抑郁药的二维相似性处于与其他在这些免疫分析中表现出弱交叉反应性的化合物相似的范围内。因此，对两种不同的尿液苯丙胺免疫分析和一种血清三环类抗抑郁药免疫分析进行了交叉反应性测试。然而，对维拉唑酮和M17代谢物的实际交叉反应性测试未检测到在浓度高达100,000 ng/mL的任何尿液苯丙胺筛查以及浓度高达2000 ng/mL的血清三环类抗抑郁药分析中存在交叉反应性。
虽然维拉唑酮代谢物M17与苯丙胺和三环类抗抑郁药具有较弱的二维结构相似性，但当前研究未证明其与两种不同的尿液苯丙胺免疫分析和一种血清三环类抗抑郁药免疫分析存在任何实验性交叉反应。幼儿摄入维拉唑酮在临床表现上与摄入苯丙胺相似，且缺乏针对维拉唑酮的常规实验室检测，这带来了诊断挑战。需要进一步开展工作以了解儿童与成人中维拉唑酮的代谢情况。
