Pitfalls and challenges associated with phenoconversion in forensic toxcicology

Purpose In recent years, several publications have demonstrated the interest and usefulness of pharmacogenetics in forensic toxicology. However, this approach remains namely focused on DNA-based phenotype, which may potentially lead to misinterpretation. Other determinants such as co-medication or physiological parameters also impact phenotype. This article aims highlight importance considering toxicology, through original case a heroin-related fatality. Method Ethanol concentration determination toxicological screening were performed using gas chromatography with flame ionization detection, liquid diode array detection mass spectrometry detection. CYP2C19 CYP2D6 genotypes determined by Taqman® real-time PCR analyses. Results Femoral blood analyses revealed presence ethanol, morphine, codeine, venlafaxine (VEN), O-desmethylvenlafaxine (ODV) N-desmethylvenlafaxine (NDV), paroxetine, risperidone. 6-acetylmorphine was identified urine. VEN, paroxetine risperidone quantified at supra-therapeutic toxic concentrations. NDV not quantified. The metabolic ratio VEN (ODV VEN) exceptionally low (about 0.7). Pharmacogenetics testing showed that patient heterozygous for CYP2C19*2 loss-of-function allele, predict an intermediate metabolism CYP2C19. None deficient alleles investigated identified. Those results suggest extensive CYP2D6-metabolism Conclusion A discrepancy seen between genomic evaluation observed VEN. tends exclude genetic origin us formulate other hypotheses, phenoconversion been induced drug interaction involving patients’ regular medications. Phenoconversion is complex phenomenon leads genotype-phenotype mismatch without any abnormality particularly described cytochromes P450 2D6 2C19. Although transient, can significant analysis interpretation genotype-focused clinical outcomes correlation toxicology conclusions.