一例拉科酰胺和米氮平自毒病例

IF 1.3 4区 医学 Q3 MEDICINE, LEGAL Legal Medicine Pub Date : 2024-05-10 DOI:10.1016/j.legalmed.2024.102457
Tadashi Nishio, Yoko Toukairin, Tomoaki Hoshi, Tomomi Arai, Makoto Nogami
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引用次数: 0

摘要

拉科萨胺是一种相对较新的抗癫痫药物,它通过选择性地使钠通道失活来发挥抗惊厥作用。自上市以来,它已被广泛用于治疗难治性癫痫,但有关其毒性或致死性血药浓度的数据却很少。在此,我们报告了一例同时自行服用大剂量拉科酰胺和米氮平的药物中毒病例。我们开发并验证了一种利用液相色谱-电喷雾离子化-串联质谱法测定尸体血液、尿液和肝脏中拉考酰胺和米氮平浓度的方法。校准曲线显示出良好的线性关系(r2 >0.995),我们的方法可重复且准确地定量,每种目标药物的测定内变异系数和测定间变异系数分别不超过10.9%和12.8%。我们使用该方法测量了一名死亡受害者血液中的药物浓度,发现拉考酰胺浓度为 91.9 μg/mL,米氮平浓度为 12.0 μg/mL。米氮平的血药浓度处于致死范围,而拉科酰胺的血药浓度约为治疗范围的 10 倍。这些药物的中枢神经系统抑制和心脏毒性协同作用可能是导致死亡的原因。我们的结论是,该病例的死因是拉科酰胺和米氮平中毒。
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A case of lacosamide and mirtazapine self-poisoning

Lacosamide is a relatively new antiepileptic drug that exerts its anticonvulsant effect by selectively inactivating sodium channels. Since its launch, it has been used widely for the treatment of intractable epilepsy, but there are scant data on the toxic or lethal blood concentrations. Here, we report a case of drug poisoning following simultaneous high-dose self-administration of lacosamide and mirtazapine. We developed and validated an approach that uses liquid chromatography coupled with electrospray ionization–tandem mass spectrometry to determine the concentrations of lacosamide and mirtazapine in cadaveric blood, urine and liver. Calibration curves showed good linearity (r2 > 0.995), and our method enabled repeatable and accurate quantification, with intra- and inter-assay coefficients of variation not exceeding 10.9 % and 12.8 %, respectively, for each target drug. We used the method to measure the drug concentrations in the blood of a dead victim and found a lacosamide concentration of 91.9 μg/mL and a mirtazapine concentration of 12.0 μg/mL. The blood mirtazapine concentration was in the lethal range, and that of lacosamide was about 10 times the therapeutic range. The synergistically central nervous system depressive and cardiotoxic effects of these drugs may have contributed to the cause of death. We concluded that the cause of death in this case was lacosamide and mirtazapine poisoning.

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来源期刊
Legal Medicine
Legal Medicine Nursing-Issues, Ethics and Legal Aspects
CiteScore
2.80
自引率
6.70%
发文量
119
审稿时长
7.9 weeks
期刊介绍: Legal Medicine provides an international forum for the publication of original articles, reviews and correspondence on subjects that cover practical and theoretical areas of interest relating to the wide range of legal medicine. Subjects covered include forensic pathology, toxicology, odontology, anthropology, criminalistics, immunochemistry, hemogenetics and forensic aspects of biological science with emphasis on DNA analysis and molecular biology. Submissions dealing with medicolegal problems such as malpractice, insurance, child abuse or ethics in medical practice are also acceptable.
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