Top

Forensic Toxicology

Published in:

01-07-2020 | Intoxication | Case Report

A fatal case of mexiletine intoxication in a 25-year-old Korean man

Authors: Ho-Sun Lee, Nam-Ye Kim, Junmo Kim

Published in: Forensic Toxicology | Issue 2/2020

Abstract

Purpose

Mexiletine is a well-known class IB antiarrhythmic agent that is primarily used for the treatment of ventricular arrhythmias. As a major route of metabolism, mexiletine is hydroxylated by cytochrome P450 2D6 (CYP2D6), forming metabolites, which have no significant antiarrhythmic activity. However, few cases of mexiletine overdose with genetic polymorphism have been reported in the literature.

Methods

We report a fatal mexiletine intoxication case of a 25-year-old Korean male. After the toxicological screening, mexiletine was initially identified by gas chromatography–mass spectrometry and subsequently confirmed by ultrahigh-performance liquid chromatography–tandem mass spectrometry.

Results

The toxicological results described the mexiletine levels in femoral and heart blood as 14.3 (range 13.6–14.6) and 22.4 (range 21.5–23.8) ng/mL, respectively. Clopidogrel was below the limit of quantification (< 0.002 ng/mL) from blood. Eight alleles were genotyped within the CYP2D6, which is the most frequently mutated gene in East Asians, including Koreans. However, no genetic mutant of CYP2D6 was observed in the case.

Conclusions

The current result was determined to be a fatal overdose of mexiletine in a young Korean man with CYP2D6 homozygous for the wild allele. A genotyping of CYP2D6 may predict the fatal dose of mexiletine in individuals.

Akinci E, Yüzbaşıoglu Y, Coşkun F (2011) Hemodialysis as an alternative treatment of mexiletine intoxication. Am J Emerg Med 29:1235.e5–6. https://doi.org/10.1016/j.ajem.2010.08.027 CrossRef

Zhu W, Mazzanti A, Voelker TL, Hou P, Moreno JD, Angsutararux P, Naegle KM, Priori SG, Silva JR (2019) Predicting patient response to the antiarrhythmic mexiletine based on genetic variation. Circ Res 124:539–552. https://doi.org/10.1161/CIRCRESAHA.118.314050 CrossRefPubMedPubMedCentral

Romman A, Salama-Hanna J, Dwivedi S (2018) Mexiletine usage in a chronic pain clinic: indications, tolerability, and side effects. Pain Phys 21:E573–E579CrossRef

Burgin A (1952) Some practical modifications to the Stas-Otto method of analysis. J Pharm Belg 7:3–9PubMed

Kim EY, Lee SS, Jung HJ, Jung HE, Yeo CW, Shon JH, Shin JG (2010) Robust CYP2D6 genotype assay including copy number variation using multiplex single-base extension for Asian populations. Clin Chim Acta 411:2043–2048. https://doi.org/10.1016/j.cca.2010.08.042 CrossRefPubMed

Lee SY, Sohn KM, Ryu JY, Yoon YR, Shin JG, Kim JW (2006) Sequence-based CYP2D6 genotyping in the Korean population. Ther Drug Monit 28:382–387. https://doi.org/10.1097/01.ftd.0000211823.80854.db CrossRefPubMed

Dorado P, Caceres M, Pozo-Guisado E, Wong ML, Licinio J, Llerena A (2005) Development of a PCR-based strategy for CYP2D6 genotyping including gene multiplication of worldwide potential use. Biotechniques 39:S571–574. https://doi.org/10.2144/000112044 CrossRefPubMed

Byeon JY, Kim YH, Lee CM, Kim SH, Chae WK, Jung EH, Choi CI, Jang CG, Lee SY, Bae JW, Lee YJ (2018) CYP2D6 allele frequencies in Korean population, comparison with East Asian, Caucasian and African populations, and the comparison of metabolic activity of CYP2D6 genotypes. Arch Pharm Res 41:921–930. https://doi.org/10.1007/s12272-018-1075-6 CrossRefPubMed

Kempton J, Manoukian A, Levine B, Smialek J (1994) A mexiletine intoxication. J Anal Toxicol 18:346–347. https://doi.org/10.1093/jat/18.6.346 CrossRefPubMed

10.

Rohrig TP, Harty LE (1994) Postmortem distribution of mexiletine in a fatal overdose. J Anal Toxicol 18:354–356. https://doi.org/10.1093/jat/18.6.354 CrossRefPubMed

11.

Jequier P, Jones R, Mackintosh A (1976) Letter: fatal mexiletine overdose. Lancet 1:429. https://doi.org/10.1016/s0140-6736(76)90272-5 CrossRefPubMed

12.

Frank SE, Snyder JT (1991) Survival following severe overdose with mexiletine, nifedipine, and nitroglycerine. Am J Emerg Med 9:43–46. https://doi.org/10.1016/0735-6757(91)90013-a CrossRefPubMed

13.

Shailesh F, Singla S, Sureddi R, Deshmukh AJ, Paydak H (2011) A patient with mexiletine-related psychosis. Int J Gen Med 4:765–766. https://doi.org/10.2147/IJGM.S25381 CrossRefPubMedPubMedCentral

14.

Bevalot F, Cartiser N, Bottinelli C, Fanton L, Guitton J (2016) Vitreous humor analysis for the detection of xenobiotics in forensic toxicology: a review. Forensic Toxicol 34:12–40. https://doi.org/10.1007/s11419-015-0294-5 CrossRefPubMed

15.

Zilg B, Thelander G, Giebe B, Druid H (2017) Postmortem blood sampling-comparison of drug concentrations at different sample sites. Forensic Sci Int 278:296–303. https://doi.org/10.1016/j.forsciint.2017.07.006 CrossRefPubMed

16.

Kupiec TC, Raj V, Vu N (2006) Pharmacogenomics for the forensic toxicologist. J Anal Toxicol 30:65–72. https://doi.org/10.1093/jat/30.2.65 CrossRefPubMed

17.

Hara Y, Nakajima M, Miyamoto KI, Yokoi T (2005) Inhibitory effects of psychotropic drugs on mexiletine metabolism in human liver microsomes: prediction of in vivo drug interactions. Xenobiotica 35:549–560. https://doi.org/10.1080/00498250500158134 CrossRefPubMed

18.

Senda C, Yamaura Y, Kobayashi K, Fujii H, Minami H, Sasaki Y, Igarashi T, Chiba K (2001) Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes. Br J Clin Pharmacol 52:100–103. https://doi.org/10.1046/j.0306-5251.2001.01411.x CrossRefPubMedPubMedCentral

19.

Bastami S, Gupta A, Zackrisson AL, Ahlner J, Osman A, Uppugunduri S (2014) Influence of UGT2B7, OPRM1 and ABCB1 gene polymorphisms on postoperative morphine consumption. Basic Clin Pharmacol Toxicol 115:423–431. https://doi.org/10.1111/bcpt.12248 CrossRefPubMed

Title: A fatal case of mexiletine intoxication in a 25-year-old Korean man
Authors: Ho-Sun Lee
Nam-Ye Kim
Junmo Kim
Publication date: 01-07-2020
Publisher: Springer Singapore
Keywords: Intoxication
Trimipramine
Published in: Forensic Toxicology / Issue 2/2020
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-020-00528-9

ACC 2024 Congress

Springer Medicine

A fatal case of mexiletine intoxication in a 25-year-old Korean man

Abstract

Purpose

Methods

Results

Conclusions

ACC 2024 Congress

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 2/2020

Identification of five mitragyna alkaloids in blood and tissues using liquid chromatography-quadrupole/time-of-flight mass spectrometry

Evaluation of 4-fluoroisobutyrylfentanyl in blood samples from 247 authentic cases submitted to the New York City Office of Chief Medical Examiner in 2017–2018

The neurotoxicity of psychoactive phenethylamines “2C series” in cultured monoaminergic neuronal cell lines

Postmortem histopathology and detection of venom by ELISA following suicide by cobra (Naja kaouthia) envenomation

Matrix-assisted laser desorption/ionization in-source decay mass spectrometry analysis of human insulin and insulin analogues for the identification of insulin from insulin preparations

Mass spectrometric characterization of carfentanil metabolism in human, dog, and rat lung microsomes via comparison to chemically synthesized metabolite standards