Association Between the Post-Mortem and Poisoning Concentration of Tramadol and Its Main Metabolite and Genotype of CYP2D6

This study was aimed to investigate the association between the metabolic ratio of Tramadol and CYP2D6 polymorphism. For this purpose, the concentrations of Tramadol and its major metabolites (as a phenotype of CYP2D6) were measured in post-mortem blood and cerebrospinal fluid (CSF) samples and Sanger sequencing of DNA was performed to identify any nucleotide variations in the exons 3 to 7 of the CYP26 gene. Finally, the correlation between sample concentrations and genotype of CYP2D6 was analyzed. In this work, 32 blood and cerebrospinal fluid (CSF) samples (29 males and 3 females) were collected from post-mortem and 12 blood samples from patients (9 males and 3 females). Sequence analyses showed CYP2D6*29, *4, and *2 in 9, 4 and 4 cases as heterozygote genotypes, respectively. Other participants had wild-type CYP2D6 tested alleles (1*). The average Tramadol concentrations (Mean ± SD) in post-mortem and patients’ plasma and CSF of cadavers were 4568.44 ± 12718.3, 11947.44 ± 7263.82, and 3805.61 ± 10633.86 (ng/mL), respectively. Also, the average concentrations of M1 in post-mortem and patients’ plasma and CSF were 1272.47 ± 2969.37, 2896.79 ± 2006.16, and 1830.68 ± 4537.89 (ng/mL), respectively. Overall, statistical analysis of the data did not show any statistically significant association between phenotype and genotype of CYP2D6. No meaningful correlation was revealed between CYP2D6 genotype and concentrations of tramadol. However, tramadol toxicity in intermediate and extensive metabolizers occurred more than in poor metabolizers, the CYP2D6 genotype can be considered among the poisoning causes of this drug.