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

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. 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. 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. 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.