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Association Between the Post-Mortem and Poisoning Concentration of Tramadol and Its Main Metabolite and Genotype of Cyp2d6 Publisher



Ahmadimanesh M1, 2 ; Mohammadi S3 ; Rouini MR4 ; Moshiri M5 ; Ahangari N6 ; Hedjazi A7 ; Sajadian M7 ; Afsharnezhad S8
Authors
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Authors Affiliations
  1. 1. Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
  2. 2. Food and Drug Control Laboratory, Food and Drug Vice Presidency, Mashhad University of Medical Sciences, Mashhad, Iran
  3. 3. Department of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Biopharmaceutics and Pharmacokinetic Division, Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
  6. 6. Department of Medical Genetic and Molecular Medicine, Mashhad University of Medical Sciences, Mshhad, Iran
  7. 7. Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran
  8. 8. Department of Biochemistry, School of Medicine, Mashhad Branch, Islamic Azad University, Mashhad, Iran

Source: Pharmaceutical Chemistry Journal Published:2023


Abstract

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. © 2023, Springer Science+Business Media, LLC, part of Springer Nature.