dextrorphan and Pneumonia

To describe the death of a toddler after a therapeutic dose of dextromethorphan and its investigation.. Case report, cytochrome P450 phenotype and genotype determination in the victim and post-mortem drug redistribution study performed in rats.. 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.. CYP450 phenotypes derived from post-mortem blood levels should be interpreted with caution and preferably confirmed by a genotype analysis.

Topics: Animals; Antitussive Agents; Cause of Death; Cytochrome P-450 CYP2D6; Dextromethorphan; Dextrorphan; Excitatory Amino Acid Antagonists; Genotype; Humans; Infant; Male; Phenotype; Pneumonia; Rats; Rats, Wistar; Tissue Distribution