Discrepancy between CYP2D6 phenotype and genotype derived from post-mortem dextromethorphan blood level
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Updated: Oct 16, 2026

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Published on: March 28, 2017
B Bailey1, R Daneman, N Daneman
1Department of Pediatrics, Division of Clinical Pharmacology and Toxicology, H¿opital Ste-Justine, 3175 Cote St. Catherine, Montr¿eal, Qu¿ebec, Canada. baileyb@med.umontreal.ca
Objective:
To describe the death of a toddler after a therapeutic dose of dextromethorphan and its investigation.
Study Design:
Case report, cytochrome P450 phenotype and genotype determination in the victim and post-mortem drug redistribution study performed in rats.
Results:
A 20-month Asian male who received 3 mg of dextromethorphan once at 09:00 h and again at 22:00 h was found dead at 04:35 h. Post-mortem examination showed signs of early bronchopneumonia (bacterial cultures were negative); dextromethorphan and dextrorphan blood concentrations taken from the heart cavity were 500 ng/ml (1. 84 micromol/l) and 200 ng/ml (0.78 micromol/l), respectively. Despite the dextromethorphan level being almost 100-fold higher than expected after therapeutic doses, intentional or unintentional overdose was extremely unlikely; other potential causes were investigated. Post-mortem drug redistribution study performed in rats showed that dextromethorphan does not undergo extensive redistribution after death (6+/-5-fold increase) and could not explain the observed dextromethorphan level. The dextromethorphan/dextrorphan concentration ratio of 2.5 found in this toddler was compatible with a slow CYP2D6 metabolizer phenotype. However, the toddler exhibited a fast metabolizer genotype. Potential reasons for this discrepancy are discussed.
Conclusion:
CYP450 phenotypes derived from post-mortem blood levels should be interpreted with caution and preferably confirmed by a genotype analysis.
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